Highly crystalline polyethylene

ABSTRACT

The present invention relates to methods for making highly crystalline polymeric material, for example, highly crystalline cross-linked and not cross-linked ultra-high molecular weight polyethylene (UHMWPE). The invention also provides methods of making additive-doped highly crystalline polymeric material using high pressure and high temperature crystallization processes, medical implants made thereof, and materials used therein.

This application claims priority to U.S. provisional application Ser.No. 60/709,796, filed Aug. 22, 2005, the entirety of which is herebyincorporated by reference.

FIELD OF THE INVENTION

The present invention relates to methods for making highly crystallinepolymeric materials, including highly crystalline oxidation-resistantcross-linked polymeric materials. Methods of crystallizing polymericmaterials under high pressure at elevated temperature and materials usedtherewith also are provided.

BACKGROUND OF THE INVENTION

Cross-linking by irradiation decreases the fatigue strength of UHMWPE.In addition, post-irradiation melting further decreases the fatiguestrength of the UHMWPE. Radiation and melting also decrease the yieldstrength, ultimate tensile strength, toughness and elongation at breakof UHMWPE.

Melting in combination with irradiation creates cross-links andfacilitates recombination of the residual free radicals trapped mostlyin the crystalline regions, which otherwise would cause oxidativeembrittlement upon reactions with oxygen. However, cross-linking and thedecrease in the crystallinity accompanying post-irradiation melting arethought to be the reasons for the decrease in fatigue strength, yieldstrength, ultimate tensile strength, toughness and elongation at breakof radiation cross-linked and melted UHMWPE. Some or all of thesechanges in properties limit the use of low wear highly cross-linkedUHMWPE to low stress applications. Therefore, a cross-linked UHMWPE withhigher crystallinity is desirable for low wear and high fatigueresistance for high stress application that require low wear.

It is, therefore, desirable to reduce the irradiation-created residualfree radical concentration in cross-linked UHMWPE without reducingcrystallinity, so as to achieve high fatigue resistance for high stressapplication that require low wear. Alternative methods to melting can beused to prevent the long-term oxidation of irradiated UHMWPE to preservehigher levels of crystallinity and fatigue strength.

The effect of crystallinity on the fatigue strength of conventionalUHMWPE is known. Investigators increased the crystallinity ofunirradiated UHMWPE by high-pressure crystallization, which increasedthe fatigue crack propagation resistance of unirradiated UHMWPE by about25% (Baker et al., Polymer, 2000, 41(2): p. 795-808). Others found thatunder high pressures (2,000-7,000 bars) and high temperatures (>200°C.), polyethylene grows extended chain crystals and achieves a highercrystallinity level (Wunderlich et al., Journal of Polymer Science PartA-2: Polymer Physics, 1969. 7(12): p. 2043-2050). High pressurecrystallization may improve the fatigue strength of irradiated UHMWPEdespite no significant changes in ultimate tensile strength (Pruitt etal., 7^(th) World Biomaterials Congress, 2004. p. 538, Bistolfi, et al.,Transactions, Orthopaedic Research Society, 2005. p. 248) through firstmelting than pressurizing. The crystallization behavior of notcross-linked or highly cross-linked polyethylene at high pressuresthrough first pressurizing, then heating at the high pressures has notbeen determined.

Polyethylene undergoes a phase transformation at elevated temperaturesand pressures from the orthorhombic to the hexagonal crystalline phase.The hexagonal phase can grow extended chain crystals and result inhigher crystallinity in polyethylene. This is believed to be aconsequence of less hindered crystallization kinetics in the hexagonalphase compared with the orthorhombic phase. One could further reduce thehindrance on the crystallization kinetics by introducing a plasticizingor a nucleating agent into the polyethylene prior to high-pressurecrystallization. The polyethylene can be doped with a plasticizingagent, for example, a-tocopherol or vitamin E, prior to high-pressurecrystallization. The doping can be achieved either by blending thepolyethylene resin powder with the plasticizing agent and consolidatingthe blend or by diffusing the plasticizing agent into the consolidatedpolyethylene. Various processes of doping can be employed as describedin U.S. application Ser. No. 10/757,551, filed Jan. 15, 2004,PCT/US/04/00857, filed Jan. 15, 2004, U.S. Provisional Application No.60/541,073, filed Feb. 3, 2004, and PCT/US2005/003305, filed Feb. 3,2005, the entireties of which are hereby incorporated by reference.

Reduction in adhesive/abrasive wear of ultra-high molecular weightpolyethylene (UHMWPE) components can be achieved by decreasing thelarge-scale deformation ability of the polymer. Cross-linking byionizing radiation is generally used for this purpose (see Muratoglu etal., J Arthroplasty, 2001, 16(2): p. 149-160; Muratoglu al.,Biomaterials, 1999, 20(16): p. 1463-1470; and McKellop et al., J OrthopRes, 1999, 17(2): p. 157-167) with a concomitant decrease in strength(Oral et al., Biomaterials, 2005).

In order to increase the strength of UHMWPE, high pressurecrystallization (HPC) of UHMWPE has been proposed (see Bistolfi et al.Transactions of the Orthopaedic Research Society, 2005, 240; Oral et al.Transactions of the Orthopaedic Research Society, 2005, p. 988, U.S.Provisional Application No. 60/541/073, filed Feb. 3, 2004, andPCT/US2005/003305, filed Feb. 3, 2005). High pressure crystallization ofunirradiated GUR1050 UHMWPE at above 160° C. and 300 MPa yielded anapproximately 70% crystalline UHMWPE, compared to 50-60% forconventional UHMWPE. This is due to a phase transition of the UHMWPEcrystals from the orthorhombic to the hexagonal phase at hightemperatures and pressures as discussed above. In the hexagonal phasecrystals grow to larger sizes and crystallinity increases (see Bassettet al, J Appl. Phys., 1974, 45(10): p. 4146-4150).

While high pressure crystallization can be used to increase the strengthof UHMWPE, it has been shown to decrease the wear resistance ofunirradiated UHMWPE (see Bistolfi et al., Transactions, OrthopaedicResearch Society, 2005, p. 240). It appears that the decrease inductility accompanying high pressure crystallization may adverselyaffect the wear resistance.

SUMMARY OF THE INVENTION

The present invention relates generally to methods of making highlycrystalline polymeric material, preferably the cross-linked material hashigher crystallinity than obtainable with previous methodologies. Morespecifically, the invention relates to methods of making highlycrystalline cross-linked UHMWPE and subsequently treating the UHMWPE toincrease its oxidation resistance. Also, the invention relates tomethods of crystallizing cross-linked ultra-high molecular weightpolyethylene (UHMWPE) under high pressure at elevated temperature in thehexagonal phase, whereby extended chain crystals are present and highcrystallinity are achieved. Also, the invention relates to methods ofcrystallizing cross-linked ultra-high molecular weight polyethylene(UHMWPE) under high pressure at elevated temperature in the hexagonalphase, whereby extended chain crystals are present and highcrystallinity are achieved followed by treating the UHMWPE to increaseits oxidation resistance. The invention also relates to methods ofcrystallizing polymeric materials including cross-linked and notcross-linked ultra-high molecular weight polyethylene (UHMWPE) underhigh pressure at elevated temperature in the hexagonal phase where highcrystallinity is achieved. Also the invention relates to methods ofincreasing the crystallinity of oxidation-resistant cross-linked and notcross-linked UHMWPE by high-pressure crystallization. The invention alsorelates to methods of crystallizing blends of polymeric materialsincluding ultra-high molecular weight polyethylene (UHMWPE) withadditives such as a plasticizing agent or an antioxidant under highpressure at elevated temperature in the hexagonal phase where highcrystallinity is achieved.

The process comprises steps of crystallizing polyethylene under highpressure at elevated temperature, irradiating at different temperaturesbelow or above the melt to control the amount of amorphous, folded andextended chain crystals during cross-linking. This invention alsorelates to processes to increase oxidation resistance where anantioxidant is incorporated into polyethylene, or a cross-linkedpolyethylene is annealed, or a high pressure and high temperatures areapplied to the cross-linked polyethylene. The processes can be usedseparately or together in various orders in accordance with theteachings herein and the skill in the at All ranges set forth herein inthe summary and description of the invention include all numbers orvalues thereabout or therebetween of the numbers of the range. Theranges of the invention expressly denominate and set forth all integersand fractional values in the range.

In one aspect, the invention provides methods of making a highlycrystalline cross-linked polymeric material comprising: a) irradiating apolymeric material with ionizing radiation, thereby forming across-linked polymeric material; b) pressurizing the cross-linkedpolymeric material under at least 10-1000 MPa; heating the pressurizedcross-linked polymeric material to a temperature below the melt of thepressurized cross-linked material; d) holding at this temperature andpressure; e) cooling the heated cross-linked polymeric material to aboutroom temperature; and f) releasing the pressure to an atmosphericpressure level, thereby forming a highly crystalline cross-linkedpolymeric material.

In another aspect, the invention provides methods of making highlycrystalline blend of polymeric material comprising: a) blending apolymeric material with an additive; b) consolidating the blend; c)pressurizing the blended polymeric material under at least 10-1000 MPa;d) heating the pressurized blended polymeric material to a temperaturebelow the melt of the pressurized blended material; e) holding at thistemperature and pressure; f) cooling the heated blended polymericmaterial to about room temperature; and g) releasing the pressure to anatmospheric pressure level, thereby forming oxidation resistant highlycrystalline blend of polymeric material.

In another aspect, the invention provides methods of making oxidationresistant highly crystalline blend of polymeric material comprising: a)blending a polymeric material with an antioxidant; b) consolidating theblend; c) pressurizing the blended polymeric material under at least10-1000 MPa; d) heating the pressurized blended polymeric material to atemperature below the melt of the pressurized blended material; e)holding at this temperature and pressure; f) cooling the heated blendedpolymeric material to about room temperature; and g) releasing thepressure to an atmospheric pressure level, thereby forming oxidationresistant highly crystalline blend of polymeric material.

In another aspect, the invention provides methods of making highlycrystalline blend of polymeric material comprising: a) blending apolymeric material with an additive; b) consolidating the blend; c)heating the blended polymeric material to a temperature above the melt;d) pressurizing the heated blended polymeric material under at least10-1000 MPa; c) holding at this temperature and pressure; f) cooling theheated blended polymeric material to about room temperature; and g)releasing the pressure to an atmospheric pressure level, thereby forminghighly crystalline blend of polymeric material.

In another aspect, the invention provides methods of making oxidationresistant highly crystalline blend of polymeric material comprising: a)blending a polymeric material with an antioxidant; b) consolidating theblend; c) heating the blended polymeric material to a temperature abovethe melt; d) pressurizing the heated blended polymeric material under atleast 10-1000 MPa; e) holding at this temperature and pressure; f)cooling the heated blended polymeric material to about room temperature;and g) releasing the pressure to an atmospheric pressure level, therebyforming oxidation resistant highly crystalline blend of polymericmaterial.

In another aspect, the invention provides methods of making oxidationresistant highly crystalline cross-linked polymeric material comprising:a) irradiating the polymeric material with ionizing radiation, therebyforming a cross-linked polymeric material; b) heating the cross-linkedpolymeric material to a temperature above the melt; c) pressurizing thecross-linked polymeric material under at least 10-1000 MPa; d) holdingat this temperature and pressure; e) cooling the heated cross-linkedpolymeric material to about room temperature; f) releasing the pressureto an atmospheric pressure level, thereby forming a highly crystallinecross-linked polymeric material; g) doping the highly crystallinecross-linked polymeric material with an antioxidant by diffusion; and h)annealing the antioxidant-doped highly crystalline cross-linkedpolymeric material at a temperature below the melting point of theantioxidant-doped cross-linked highly crystalline polymeric material,thereby forming oxidation resistant highly crystalline cross-linkedpolymeric material.

In another aspect, the invention provides methods of making, oxidationresistant highly crystalline cross-linked polymeric material comprising:a) irradiating the polymeric material with ionizing radiation, therebyforming a cross-linked polymeric material; b) pressurizing thecross-linked polymeric material under at least 10-1000 MPa; c) heatingthe pressurized cross-linked polymeric material to a temperature belowthe melting point of the pressurized cross-linked polymeric material; d)holding at this temperature and pressure; e) cooling the heatedcross-linked polymeric material to about room temperature; f) releasingthe pressure to an atmospheric, pressure level, thereby forming a highlycrystalline cross-linked polymeric material; g) doping the highlycrystalline cross-linked polymeric material with an antioxidant bydiffusion; and h) annealing the antioxidant-doped highly crystallinecross-linked polymeric material at a temperature below the melting pointof the polymeric material, thereby forming oxidation resistant highlycrystalline cross-linked polymeric material.

In another aspect, the invention provides methods of making a highlycrystalline cross-linked polymeric material comprising the steps of a)heating the polymeric material to a temperature above the melt; b)pressurizing the polymeric material under at least 10-1000 MPa; c)holding at this temperature and pressure; d) cooling the heatedpolymeric material to about room temperature; e) releasing the pressureto an atmospheric pressure level, thereby forming a highly crystallinepolymeric material; f) irradiating the highly crystalline polymericmaterial melt with ionizing radiation, thereby forming a cross-linkedhighly crystalline polymeric material; and g) annealing the cross-linkedhighly crystalline is polymeric material below the melt.

In another aspect, the invention provides methods of making a highlycrystalline cross-linked polymeric material comprising the steps of: a)heating the polymeric material to a temperature above the melt; b)pressurizing the polymeric material under at least 10-1000 MPa; c)holding at this temperature and pressure; d) cooling the heatedpolymeric material to about room temperature; e) releasing the pressureto an atmospheric pressure level, thereby forming a highly crystallinepolymeric material; f) irradiating the highly crystalline polymericmaterial melt with ionizing radiation, thereby forming a cross-linkedhighly crystalline polymeric material; and g) heating the cross-linkedhighly crystalline polymeric material above the melting point.

In another aspect, the invention provides methods of making highlycrystalline polymeric material comprising: a) doping the polymericmaterial with an additive by diffusion; h) heating the polymericmaterial to a temperature of above the melting point of the polymericmaterial; c) pressuring the heated polymeric material under at least10-1000 MPa d) holding at this pressure and temperature; e) cooling theheated polymeric material to about room temperature; and f) releasingthe pressure to about an atmospheric pressure level, thereby forming ahighly crystalline polymeric material.

In another aspect, the invention provides methods of making highlycrystalline polymeric material comprising: a) doping the polymericmaterial with an additive by diffusion; b) pressuring the polymericmaterial under at least 10-1000 MPa; c) heating the pressurizedpolymeric material to a temperature of above 100° C. to below the meltof the pressurized polymeric material; d) holding at this pressure andtemperature; e) cooling the heated polymeric material to about roomtemperature; and f) releasing the pressure to about an atmosphericpressure level, thereby forming a highly crystalline polymeric material.

In another aspect, the invention provides methods of making cross-linkedhighly crystalline polymeric material comprising: a) doping thepolymeric material with an additive by diffusion; b) heating thepolymeric material to a temperature of above the melting point of thepolymeric material; c) pressuring the heated polymeric material under atleast 10-1000 MPa; d) holding at this pressure and temperature; e)cooling the heated polymeric material to about room temperature; f)releasing the pressure to about an atmospheric pressure level, therebyforming a highly crystalline polymeric material; and g) irradiating thehighly crystalline polymeric material with ionizing radiation, therebyforming a highly crystalline cross-linked polymeric material.

In another aspect, the invention provides methods of making cross-linkedhighly crystalline polymeric material comprising: a) doping thepolymeric material with an additive by diffusion; b) pressuring thepolymeric material under at least 10-1000 MPa; c) heating thepressurized polymeric material to a temperature of above 100° C. tobelow the melt of the pressurized polymeric material; d) holding at thispressure and temperature; e) cooling the heated polymeric material toabout room temperature; f) releasing the pressure to about anatmospheric pressure level, thereby forming a highly crystallinepolymeric material; and g) irradiating the highly crystalline polymericmaterial with ionizing radiation, thereby forming a highly crystallinecross-linked polymeric material.

In another aspect, the invention provides methods of making highlycrystalline polymeric material comprising; a) irradiating the polymericmaterial with ionizing radiation, thereby forming a cross-linkedpolymeric material; b) doping the cross-linked polymeric material withan additive by diffusion; c) heating the crosslinked polymeric materialto a temperature of above the melting point of the crosslinked polymericmaterial; d) pressuring the heated crosslinked polymeric material underat least 10-1000 MPa; e) holding at this pressure and temperature; f)cooling the heated crosslinked polymeric material to about roomtemperature; and g) releasing the pressure to about an atmosphericpressure level, thereby forming a highly crystalline crosslinkedpolymeric material.

In another aspect, the invention provides methods of making cross-linkedhighly crystalline polymeric material comprising: a) irradiating thepolymeric material with ionizing radiation, thereby forming across-linked polymeric material; b) doping the cross-linked polymericmaterial with an additive by diffusion; b) pressuring the cross-linkedpolymeric material under at least 10-1000 MPa; c) heating thepressurized cross-linked polymeric material to a temperature of above100° C. to below the melt of the pressurized cross-linked polymericmaterial; d) holding at this pressure and temperature; e) cooling theheated cross-linked polymeric material to about room temperature; and f)releasing the pressure to about an atmospheric pressure level, therebyforming a highly crystalline cross-linked polymeric material.

In another aspect, the invention provides methods of making highlycrystalline polymeric material comprising: a) doping the polymericmaterial with an additive by diffusion; b) annealing the polymericmaterial below or above the melt; c) heating the polymeric material to atemperature of above the melting point of the polymeric material; d)pressuring the heated polymeric material under at least 10-1000 MPa; e)holding at this pressure and temperature; f) cooling the heatedpolymeric material to about room temperature; and g) releasing thepressure to about an atmospheric pressure level, thereby forming ahighly crystalline polymeric material.

In another aspect, the invention provides methods of making highlycrystalline polymeric material comprising: a) doping the polymericmaterial with an additive by diffusion; b) annealing the polymericmaterial below or above the melt; c) pressuring the polymeric materialunder at least 10-1000 MPa; d) heating the pressurized polymericmaterial to a temperature of above 100° C. to below the melt of thepressurized polymeric material; e) holding at this pressure andtemperature; f) cooling the heated polymeric material to about roomtemperature; and g) releasing the pressure to about an atmosphericpressure level, thereby forming a highly crystalline polymeric material.

In another aspect, the invention provides methods of making highlycrystalline cross-linked polymeric material comprising: a) doping thepolymeric material with an additive by diffusion; b) annealing thepolymeric material below or above the melt; c) heating the polymericmaterial to a temperature of above the melting point of the polymericmaterial; d) pressuring the heated polymeric material under at least10-1000 MPa; e) holding at this pressure and temperature; f) cooling theheated polymeric material to about room temperature; g) releasing thepressure to about an atmospheric pressure level, thereby forming ahighly crystalline polymeric material; and h) irradiating the highlycrystalline polymeric material with ionizing radiation, thereby forminga cross-linked highly crystalline polymeric material.

In another aspect, the invention provides methods of making highlycrystalline cross-linked polymeric material comprising: a) doping thepolymeric material with an additive by diffusion; b) annealing thepolymeric material below or above the melt; c) pressuring the polymericmaterial under at least 10-1000 MPa; d) heating the pressurizedpolymeric material to a temperature of above 100° C. to below the meltof the pressurized polymeric material; e) holding at this pressure andtemperature; f) cooling the heated polymeric material to about roomtemperature; g) releasing the pressure to about an atmospheric pressurelevel, thereby forming a highly crystalline polymeric material; and h)irradiating the highly crystalline polymeric material with ionizingradiation, thereby funning a cross-linked highly crystalline polymericmaterial.

In another aspect, the invention provides methods of making highlycrystalline polymeric material comprising; a) irradiating the polymericmaterial with ionizing radiation, thereby forming a cross-linkedpolymeric material; b) doping the cross-linked polymeric material withan additive by diffusion; c) annealing the cross-linked polymericmaterial below or above the melt; d) heating the crosslinked polymericmaterial to a temperature of above the melting point of the crosslinkedpolymeric material; e) pressuring the heated crosslinked polymericmaterial under at least 10-1000 MPa; f) holding at this pressure andtemperature; g) cooling the heated crosslinked polymeric material toabout room temperature; and h) releasing the pressure to about anatmospheric pressure level, thereby forming a highly crystallinecrosslinked polymeric material.

In another aspect, the invention provides methods of making cross-linkedhighly crystalline polymeric material comprising: a) irradiating thepolymeric material with ionizing radiation, thereby forming across-linked polymeric material; b) doping the cross-linked polymericmaterial with an additive by diffusion; c) annealing the cross-linkedpolymeric material below or above the melt; d) pressuring thecross-linked polymeric material under at least 10-1000 MPa; e) heatingthe pressurized cross-linked polymeric material to a temperature ofabove 100° C. to below the melt of the pressurized cross-linkedpolymeric material; f) holding at this pressure and temperature; g)cooling the heated cross-linked polymeric material to about roomtemperature; and h) releasing the pressure to about an atmosphericpressure level, thereby forming a highly crystalline cross-linkedpolymeric material.

In another aspect, the invention provides irradiated or unirradiatedblend of UHMWPE with an additive, wherein the blend of the UHMWPE andadditive is machined to form a finished product, for example, anarticle, an implant, or a medical prosthesis and the like, and whereinthe finished product is high pressure crystallized. High pressurecrystallization is carried out by heating to a temperature above themelting point of the irradiated or unirradiated UHMWPE at ambientpressure, pressurizing to at least about 10-1000 MPa, preferably atleast about 150 MPa, more preferably at least about 250 MPa, heating toa temperature above the melting point, cooling to about room temperatureand releasing the pressure. High pressure crystallization also can becarried out by pressurizing to at least about 10-1000 MPa, preferably atleast about 150 MPa, more preferably at least about 250 MPa, heating toa temperature above the melting point of the irradiated or unirradiatedUHMWPE at ambient pressure and below the melting point of thepressurized irradiated or unirradiated UHMWPE, cooling to about roomtemperature, and releasing the pressure. The finished product can bepackaged and sterilized.

In another aspect, the invention provides UHMWPE incorporated with anadditive by either doping by diffusion or by blending with powder andconsolidation of the blend, wherein the UHMWPE is high pressurecrystallized. High pressure crystallization is carried out by heating toa temperature above the melting point of the irradiated or unirradiatedUHMWPE at ambient pressure, pressurizing to at least about 10-1000 MPa,preferably at least about 150 MPa, more preferably at least about 250MPa, heating to a temperature above the melting point, cooling to aboutroom temperature and releasing the pressure. High pressurecrystallization also can be carried out by pressurizing to at leastabout 10-1000 MPa, preferably at least about 150 MPa, more preferably atleast about 250 MPa, heating to a temperature above the melting point ofthe irradiated or unirradiated UHMWPE at ambient pressure and below themelting point of the pressurized irradiated or unirradiated UHMWPE,cooling to about room temperature, and releasing the pressure. Afinished product can be machined. The finished product can be packagedand sterilized.

In another aspect, the invention provides cross-linked UHMWPEincorporated with an additive by either doping by diffusion or byblending with powder and consolidation of the blend, wherein the UHMWPEis high pressure crystallized and irradiated. In another aspect, theinvention provides cross-linked UHMWPE incorporated with an additive byeither doping by diffusion or by blending with powder and consolidationof the blend, wherein the UHMWPE is irradiated and high pressurecrystallized.

Unless otherwise defined, all technical and scientific terms used hereinin their various grammatical forms have the same meaning as commonlyunderstood by one of ordinary skill in the art to which this inventionbelongs. Although methods and materials similar to those describedherein can be used in the practice or testing of the present invention,the preferred methods and materials are described below. In case ofconflict, the present specification, including definitions, willcontrol. In addition, the materials, methods, and examples areillustrative only and are not limiting.

Further features, objects, and advantages of the present invention areapparent in the claims and the detailed description that follows. Itshould be understood, however, that the detailed description and thespecific examples, while indicating preferred aspects of the invention,are given by way of illustration only, since various changes andmodifications within the spirit and scope of the invention will becomeapparent to those skilled in the art from this detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A shows schematically the high-pressure crystallization (“HPC”)process and phases of polyethylene under various temperature andpressure conditions.

FIG. 1B shows a heating and pressurization scheme where the sample isfirst heated to above the melting temperature at ambient pressure to thehigh pressure crystallization temperature and pressurized to transitionto the hexagonal phase from the melt phase.

FIG. 1C shows a heating and pressurization scheme where the sampleheated to above the melting temperature to the high pressurecrystallization temperature and concurrently pressurized to transitionto the hexagonal phase from the melt phase.

FIG. 1D shows a heating and pressurization scheme where the sample ispressurized to slightly below the triple point pressure, then heated toabove the melt, then pressurized further to transition to the hexagonalphase from the melt phase.

FIG. 1F shows a heating and pressurization scheme where the sample ispressurized and heated in subsequent steps transitioning in and out ofthe melt and orthorhombic phases until the triple point pressure andtemperature, then it is heated and pressurized to transition to thehexagonal phase from the melt phase.

FIG. 1F shows a heating and pressurization scheme where the sample isheated to above the desired high pressure crystallization temperatureand subsequently cooled and pressurized at the same time to transitioninto the hexagonal phase from the melt phase.

FIG. 1G shows a heating and pressurization scheme where the sample isheated and pressurized at the same time to about the desired highpressure crystallization pressure, then heated such that the sample ismelted at this pressure and then cooled and further pressurized ifdesired to transition into the hexagonal phase from the melt phase.

FIG. 1H shows a heating and pressurization scheme where the sample ispressurized to about the desired high pressure annealing pressure andheated to transition to the hexagonal phase from the orthorhombic phase.

FIG. 1I shows a heating and pressurization scheme where the sample isconcurrently heated and pressurized to transition to the hexagonal phasefrom the orthorhombic phase.

FIG. 1J shows a heating and pressurization scheme where the sample isconcurrently heated and pressurized to transition to the hexagonal phasefrom the orthorhombic phase.

FIG. 1K shows a heating and pressurization scheme where the sample isheated to below the melt at ambient pressure, then concurrently heatedand pressurized to the the desired high pressure annealing pressure andbelow the phase transition temperatures at this pressure, then it isfurther heated to transition to the hexagonal phase from theorthorhombic phase.

FIG. 1L shows a heating and pressurization scheme where the sample isheated and pressurized in subsequent steps to transition to thehexagonal phase from the orthorhombic phase.

FIG. 1M shows a heating and pressurization scheme where the sample isheated and pressurized in subsequent steps comprising heating andconcurrent cooling and pressurization to transition to the hexagonalphase from the orthorhombic phase.

FIG. 1N shows a heating and pressurization scheme where the sample isheated and pressurized to a pressure above the desired high pressureannealing pressure in the orthorhombic phase, then heated anddepressurized to transition to the hexagonal phase from the orthorhombicphase.

FIG. 1O shows a cooling and depressurization scheme where the sample iscooled to about room temperature at the high pressure crystallization orannealing pressure to transition from the hexagonal phase to theorthorhombic phase and the pressure is subsequently released in theorthorhombic phase.

FIG. 1P shows a cooling and depressurization scheme where the sample iscooled to about below the melting temperature at ambient pressure anddepressurized to transition from the hexagonal phase into theorthorhombic phase, then further cooled at ambient pressure to aboutroom temperature in the orthorhombic phase.

FIG. 1Q shows a cooling and depressurization scheme where the sample iscooled and depressurized in subsequent steps to transition from thehexagonal phase to the orthorhombic phase and eventually to ambientpressure and about room temperature in the orthorhombic phase.

FIG. 1R shows a cooling and depressurization scheme where the sample iscooled to at the high pressure crystallization or annealing pressure totransition from the hexagonal phase into the orthorhombic phase to atemperature above the melting point at ambient pressure, held at thistemperature while depressurizing in the orthorhombic phase, then furthercooled to about room temperature and depressurized to ambient pressurein the orthorhombic phase.

FIG. 1S shows a cooling and depressurization scheme where the sample iscooled at the high pressure crystallization or annealing pressure totransition from the hexagonal phase into the orthorhombic phase to atemperature below the melting point at ambient pressure, held at thistemperature while depressurizing in the orthorhombic phase, then furthercooled to about room temperature in the orthorhombic phase.

FIG. 1T shoes a cooling and depressurization scheme where the sample iscooled at the high pressure crystallization or annealing pressure totransition from the hexagonal phase into the orthorhombic phase to atemperature about the melting point at ambient pressure, held at thistemperature while depressurizing in the orthorhombic phase to about thetriple point pressure, then further cooled to about room temperature anddepressurized to about ambient pressure in the orthorhombic phase.

FIG. 1U shows a cooling and depressurization scheme where the sample iscooled at the high pressure crystallization or annealing pressure totransition from the hexagonal phase into the orthorhombic phase to atemperature about the melting point at ambient pressure, pressurized atthis temperature in the orthorhombic phase, then depressurized to aboutambient pressure and then further cooled to about room temperature inthe orthorhombic phase.

FIG. 1V shows a cooling and depressurization scheme where the sample iscooled to transition from the hexagonal phase into the orthorhombicphase and eventually to ambient pressure and temperature comprisingpressurization in the orthorhombic phase.

FIG. 1W shows a cooling and depressurization scheme where the sample iscooled, then concurrently heated and depressurized in a stepwise mannerto transition from the hexagonal phase into the orthorhombic phase andeventually to ambient pressure and temperature in the orthorhombicphase.

FIG. 2 schematically shows various steps and methods of making highlycrystalline oxidation-resistant cross-linked polymeric material.

FIG. 3 shows DSC analysis of HPC treated cross-linked polyethyleneobtained through Route I and Route II treatments compared to non-HPCtreated cross-linked UHMWPE.

FIGS. 4( a-d) depict SEM images of freeze fracture surfaces of highpressure crystallized virgin (a), 0.1 wt % (b), 0.3 wt % (c), 1.0 wt %α-tocopherol-blended UHMWPE.

FIGS. 5( a-d) illustrate SEM images of freeze fracture surfaces ofvirgin (a), 0.1 wt % (b), 0.3 wt % (c), 1.0 wt % a-tocopherol-blendedUHMWPE.

FIG. 6 shows α-tocopherol profiles in high pressure crystallized,irradiated, α-tocopherol doped and homogenized UHMWPE. The graph showsthe region from the surface to the center of the sample, where theconcentration of α-tocopherol is lowest.

FIG. 7 depicts a TEM image of 0.1 wt % Vitamin E-blended HPC UHMWPE.

DETAILED DESCRIPTION OF THE INVENTION

The invention provides methods of making highly crystalline cross-linkedand not cross-linked polymeric material, medical implants made thereof;which comprise medical devices, including permanent and non-permanentmedical devices. The invention also provides methods of making oxidationresistant highly crystalline cross-linked and not cross-linked polymericmaterial and medical implants made thereof including permanent andnon-permanent medical devices. The invention pertains to methods ofcrystallizing polyethylene, such as UHMWPE, under high pressure atelevated temperature, irradiating at different temperatures, doping thecross-linked polyethylene with an antioxidant. The invention alsopertains to methods of blending polyethylene with an additive, such asVitamin E, crystallizing the blend, irradiating at differenttemperatures including below or above the melting point of polyethyleneunder normal or pressured conditions. The invention also pertains tomethods of incorporating polyethylene with an additive, such as VitaminE, and crystallizing the additive-incorporated polymeric material.

Wear resistance in UHMWPE is achieved through a decrease in its largestrain deformation ability. Cross-linking is a means of achieving adecrease in large-strain deformation by limiting the mobility of thepolymer chains during deformation. While high pressure crystallization(HPC) can be used to increase the strength of UHMWPE, it may adverselyaffect the wear resistance, presumably due to an increase in stiffness.Therefore, to counteract this, according to one aspect of the invention,a plasticizing agent is used in UHMWPE during high pressurecrystallization. The use of a plasticizing agent, such as Vitamin E,during the high pressure crystallization counteracts the decrease inmobility of the chains accompanying the increase in crystallinityobtained by high pressure crystallization. Therefore, incorporation of aplasticizing agent decreases the wear rate of high pressure crystallizedUHMWPE and results in higher crystallinity and higher strength. Thisfinding is a paradigm shift in that the reduction in wear need not beachieved by cross-linking and need not be accompanied by a reduction instrength.

Incorporation of a plasticizing agent, such as vitamin E, into UHMWPEcan be achieved in different ways, for example, a) by blending withUHMWPE powder and consolidation of the plasticizing agent and UHMWPE;and b) by diffusion of the plasticizing agent into consolidated solidstock, preform or a finished product made of UHMWPE. In order toincrease the uniformity of the plasticizing agent in the UHMWPE, theUHMWPE is doped by diffusion followed by annealing at a temperaturebelow or above the melt at ambient pressure or under pressure.

Polyethylene is a semi-crystalline material (55-60%) and contains foldedchain crystals when crystallized from the melt under ambient pressures.The majority of the crystals are in the orthorhombic phase with latticedimensions of 7.42, 4.95, and 2.55 Å for a, b and c dimensions,respectively. The unit cell axes are at 90° to each other. Deformationgives rise to the monoclinic phase with lattice dimensions of 8.09,4.79, and 2.55 Å. In the hexagonal phase, which is only encountered atpressures in excess of 300 MPa (see FIGS. 1A-1W, for example), the unitcell dimensions become 8.42, 4.56, and <2.55 Å. In this phase, theindividual chain stems are rotated at random phase angles with respectto each other allowing for chains to slide past each other to form adensely packed structure. The crystals in this phase are termed the‘Extended Chain Crystals’ (ECC) because the dense packing allows thecrystals to grow to a larger extent than folded chain crystals.

It is known that the crystallinity of not cross-linked UHMWPE can beincreased by high pressure and high temperature crystallization. Forinstance, when crystallized not cross-linked UHMWPE at pressures above300 MPa and 160° C. to obtain the hexagonal phase transition, the peakmelting point of the crystals, as determined by differential scanningcalorimetry (DSC), shifted to higher temperatures and the overallcrystallinity increased. Not cross-linked high pressure crystallizedpolyethylene with high crystallinity appeared to have higher fatigueresistance as a function of increasing crystallinity (see Baker et al.,Polymer, 2000, 41(2): p. 795-808). Therefore, an object of the inventionwas to achieve a wear resistant highly crystalline polyethylene(with >51% crystallinity) with good fatigue and oxidation resistance.

High pressure crystallization is generally referred to as all of themethods of allowing the formation of extended chain crystals in thehexagonal phase. This transformation can be done by several differentmethods. The first is by heating to a temperature above the meltingpoint of the polyethylene at ambient pressure, then pressurizing so thatthe sample is in the melt during the pressurization until the conditionsare met for the melt-to-hexagonal transition to occur. Alternatively,stepwise heating and pressurization is preformed such that the sample isnot always in the melt until close to the hexagonal phase. The sampleheating and pressurization can be done in a variety of manners such thatwhen the hexagonal phase transformation occurs, the UHMWPE does not havea substantial amount of preformed crystals and is considered in the meltphase.

Once the conditions are met for the hexagonal phase to be achieved andthe extended chain crystals are formed, the sample cannot be allowed tocompletely melt because the desired crystalline structure would be lost.Therefore, any cooling and depressurization scheme allowing the sampleto stay in the hexagonal or orthorhombic regions is used. For example, asample high pressure crystallized at 200° C. and 380 MPa (55,000 psi) iscooled down to approximately below the melting point of polyethylene atroom temperature about 135-140° C.), then the pressure is released.Alternatively, a to stepwise cooling and depressurization method is usedas lone as the sample does not melt substantially.

The ratio of orthorhombic to hexagonal crystals may be dependent on thetime spent in the hexagonal phase and whether or not the sample hasmelted during the cool down. If a sample is fully crystallized in thehexagonal phase, is cooled down and/or depressurized is to a pressuresuch that it encounters the melt phase partially or completely, andsolely decreasing the temperature at the new pressure would not causethe sample to be in the hexagonal phase then some or all of the crystalswould be converted to orthorhombic crystals when the sample is furthercooled down and depressurized.

High toughness and high fatigue strength of polymers are attributed toenergy absorbing mechanisms such as cavitation and plastic deformation.The major energy absorbing mechanism in polyethylene is the plasticdeformation of the crystalline domains (crystal plasticity), whichdepends on ductility and crystallinity. Cross-linking polyethylene withhigh dose levels of irradiation drastically reduces the mobility of thechains, hence reducing the overall ductility. Melting in the presence ofcross-links limits the ability of the chains to reorder and hencedecreases the crystallinity of polyethylene. The combination of thesetwo factors, namely reduced chain mobility and reduced crystallinity,reduces cross-linked and melted polyethylene's fatigue resistance.

According to the invention, highly crystalline wear-resistantpolyethylene can be obtained following various processes and steps, asdescribed below, for example:

1. Incorporating a plasticizing agent into unirradiated or irradiatedpolyethylene by either one of the following methods:

-   -   A. Blending with plasticizing agent and consolidating;    -   B. Doping with plasticizing agent by diffusion, and annealing at        a temperature above or below the melt;

2. High pressure crystallized (HPC) the polyethylene using either RouteI or Route II:

A. Route I: Heat to the desired temperature, for example, above the melt(for example, about 140° C., about 160° C., about 180° C., about 200°C., about 250° C., or about 300° C.); then pressurize; then holdpressure at about the same pressure, for one minute to a day or more,preferably about 0.5 hours to 12 hours, more preferably 1 to 6 hours;then release the pressure (pressure has to be released after coolingdown to room temperature to avoid melting of the crystals achieved underhigh pressure).

B. Route II: Pressurize to the desired pressure; then heat to thedesired temperature, for example, below the melt of pressurizedpolyethylene (for example, about 150° C., about 160° C., about 180° C.,about 195° C. about 225° C., about 300° C. and about 320° C.); then holdpressure at about the same pressure, for one minute to a day or more,preferably about 0.5 hours to 12 hours, more preferably 1 to 6 hours;then cool to room temperature; then release the pressure (pressure hasto be released after cooling down to room temperature to avoid meltingof the crystals achieved under high pressure).

According to the invention, highly crystalline cross-linkedoxidation-resistant polyethylene can be obtained following variousprocesses and steps (see FIG. 2, for example), as described below, forexample:

1. High pressure crystallized (HPC) unirradiated and not cross-linkedpolyethylene using either Route I or Route II:

-   -   A. Route I: Heat to the desired temperature, for example, above        the melt (for example, about 140° C., about 160° C., about 180°        C., about 200° C., about 250′C., or about 300° C.); then        pressurize; then hold pressure at about the same pressure, for        one minute to a day or more, preferably about 0.5 hours to 12        hours, more preferably 1 to 6 hours; then release the pressure        (pressure has to be released after cooling down to room        temperature to avoid melting of the crystals achieved under high        pressure).    -   B. Route II: Pressurize to the desired pressure; then heat to        the desired temperature, for example, below the melt of        pressurized polyethylene (for example, about 150° C., about 160°        C., about 180° C., about 195° C., about 225° C. about 300° C.        and about 320° C.); then hold pressure at about the same        pressure, for one minute to a day or more, preferably about 0.5        hours to 12 hours, more preferably 1 to 6 hours; then cool to        room temperature; then release the pressure (pressure has to be        released after cooling down to room temperature to avoid melting        of the crystals achieved under high pressure).

2. Then irradiate the high-pressure crystallized (HPC) polyethyleneusing either cold or warm irradiation:

-   -   A. Cold Irradiation (CI): irradiate at between about room        temperature and 90° C. using either e-beam or gamma radiation.        If the crystallinity of the HPC-polyethylene is too high, there        may not be enough amorphous polyethylene available for        cross-linking. Therefore, it may require higher than usual dose        levels, that is the dose levels required for polyethylene        crystallized without high-pressure (as described herein, for        example, usual dose levels of 75 kGy or 100 kGy), to achieve a        desired wear resistance or crosslink density.    -   B. Warm Irradiation (WI): irradiate at between about 90° C. and        the peak melting point of HPC-polyethylene, which is generally        around 145° C. The temperature of irradiation can be adjusted to        achieve a desired extent of amorphous polyethylene during        irradiation.

3. Then treat the irradiated HPC-polyethylene (1-HPC) by either one offollowing methods or a combination thereof:

-   -   A. Repeat the high-pressure crystallization following Route I or        Route II, as described above. a Dope with an antioxidant, such        as vitamin E, which can be done by various ways, for example,        -   i. machine the final product, soak in an antioxidant, such            as a vitamin E solution, at between room temperature and            boiling point of vitamin E solution; then wash, package and            sterilize with either gas plasma, ethylene oxide, or            ionizing radiation, such as gamma either in air or in inert            gas.        -   ii. soak highly crystalline polymeric material in an            antioxidant, such as a vitamin E solution, at between room            temperature and boiling point of vitamin E solution; machine            medical implant, then wash, package and irradiate packaged            medical implant to cross-link and sterilize.    -   C. Treat with a CIMA (Cold Irradiation and Mechanically        Annealed) method, for example,        -   i. heat: to a temperature between 90° C. and peak melting            point of HPC, deform under compression to a compression            ratio of above 2.5, hold deformation and 1.5 Cool to room            temperature, anneal at a temperature between 90° C. and peak            melting point of I-HPC, machine the final product, package            and sterilize, preferably sterilize with ethylene oxide or            gas plasma. CIMA methods can be applied as described in US            Patent publication 20030149125 (U.S. application Ser. No.            10/252,582), filed Sep. 24, 2002, the entirety of which is            hereby incorporated by reference.

In one aspect of the invention, the polymeric material is heated to atemperature above the melting point, for example, about 140° C., about160° C., about 180° C., about 200° C., about 250° C., or about 300° C.during the Route I high pressure crystallization.

In another aspect, the polymeric material is heated to a temperaturebelow the melting point of the pressurized polymeric material, forexample, about 150° C., about 160° C., about 180° C., about 195° C.,about 225° C., about 300° C., and about 320° C. during the Route II highpressure crystallization.

An antioxidant, which is compatible with lipophilic polyethylene, blendswell with and protects irradiated polyethylene :against oxidation, atradiation doses as high as 100 KGy. Moreover, antioxidant was found notto interfere with cross-linking of polyethylene, when diffused afterirradiation. Therefore, cross-linked polyethylene diffused withantioxidant after irradiation showed wear rates comparable tocontemporary cross-linked and melted polyethylenes. Mechanicaldeformation at temperatures below the melt also is an alternativeapproach of removing residual free radicals from irradiated polyethylenewithout melting.

The present invention also provides methods of crystallizing a blend ofpolymer with an additive under a high pressure and high temperatures andirradiating thus formed highly crystalline blend to obtain a highlycrystalline, cross-linked blend of polymer and the additive. The presentinvention also provides methods of crystallizing a blend of polymer withadditive, which is also an antioxidant, under a high pressure and hightemperatures and irradiating thus formed highly crystalline blend toobtain a highly crystalline, cross-linked oxidation-resistant blend ofpolymer and an additive, which is also an antioxidant,

The present invention also provides methods of improving the oxidationresistance of highly crystalline cross-linked UHMWPE without melting.Melting of the highly crystalline UHMWPE will eliminate the FCC andreduce the crystallinity of the polymer. Therefore, the presentinvention provides the methods that use antioxidant or mechanicaldeformation below the melting point. According to the invention,improvement of oxidation resistance can be achieved either by dopingwith an antioxidant as described herein or by mechanical deformationmethods. The mechanical deformation is used after irradiation to reducethe population of residual free radicals without melting the polymer,for example, uniaxially compressing to a compression ratio of at least2.0 below the melting point (for example, less than about 150° C.) isutilized to reduce the residual free radical concentration. According tothe invention, orientation and some of the thermal stresses that canpersist following the mechanical deformation are reduced by furtherannealing at an elevated temperature below the melting point and coolingdown. Following annealing, it may be desirable to cool down thepolyethylene at slow enough cooling rate (for example, at about 10°C./hour) so as to minimize thermal stresses.

As described herein, it is demonstrated that mechanical deformation caneliminate residual free radicals in a radiation cross-linked UHMWPE. Theinvention also provides that one can first deform UHMWPE to a new shapeeither at solid- or at molten-state, for example, by compression.According to a process of the invention, mechanical deformation ofUHMWPE when conducted at a molten-state, the polymer is crystallizedunder load to maintain the new deformed shape. Following the deformationstep, the deformed UHMWPE sample is irradiated at a temperature belowthe melting point to crosslink, which generates residual free radicals.To reduce or eliminate these free radicals, the irradiated polymerspecimen is heated to a temperature below the melting point of thedeformed and irradiated polyethylene (for example, up to about 150° C.)to allow for the shape memory to partially recover the original shape.Generally, it is expected to recover about 80-90% of the original shape.During this recovery, the crystals undergo motion, which can help thefree radical recombination and elimination. The above process is termedas a ‘reverse-IBMA’. The reverse-IBMA (reverse-irradiation below themelt and mechanical annealing) technology can be a suitable process interms of bringing the technology to large-scale production ofUHMWPE-based medical devices.

In one aspect, the invention discloses medical implants, includingpermanent and non-permanent medical devices, comprising polymericmaterial having high crosslink density, high crystallinity, wear andoxidation resistance comparable with a highly cross-linked and meltedpolyethylene with fatigue resistance above highly cross-linked andmelted polyethylene.

Medical implants, as disclosed herein can be obtained by variousprocesses disclosed herein, for example, consolidating polymericmaterial; crystallizing the consolidated polymeric material under a hightemperature, such as at above 150° C. and at a high pressure, such as atabove 10-1000 MPa (for example, at least about 150 MPa, 200 MPa, 250MPa, 300 MPa, 310 MPa, 320 MPa, 380 MPa, 400 MPa, or 450 MPa),preferably at least about 150 MPa, more preferably at least about 250MPa, subsequently, cooling down to room temperature followed by reducingthe pressure to ambient, subsequently heating and holding the highpressure crystallized polymeric material at a certain temperature, suchas at below 150° C., so as to achieve partly amorphous polyethylene;irradiating by ionizing radiation to a dose of more than 1 kGy, such asabout 25-400 kGy or more, preferably to above about 75 kGy, morepreferably about 100 kGy; yet more preferably about 150 kGy; increasingthe oxidation resistance by either doping with an antioxidant ordecreasing the concentration of residual free radicals, for example, bymechanical deformation and annealing and/or crystallizing under highpressure and temperature.

Crystallization under high pressure is done by first melting thepolyethylene at low pressure, subsequently pressurizing to above 10-1000MPa (for example, at least about 150 MPa, 200 MPa, 250 MPa, 300 MPa, 310MPa, 320 MPa, 380 MPa, 400 MPa, or 450 MPa), preferably at least about150 MPa, more preferably at least about 250 MPa, and cooling to aboutroom temperature; or by first pressurizing to above 10-1000 MPa (forexample, at to least about 150 MPa, 200 MPa, 250 MPa, 300 MPa, 310 MPa,320 MPa, 380 MPa, 400 MPa, or 450 MPa), preferably at least about 150MPa, more preferably at least about 250 MPa, then increasing thetemperature until orthorhombic to hexagonal phase transition occurs,then cooling down and depressurizing.

The holding time in the melt, the holding time under pressure, theultimate temperature and pressure and the cooling rate can be changed toobtain the highest crystallinity and a roughly equal amount of extendedand folded chain crystals.

The temperature at which the folded chain crystals of the high pressurecrystallized polyethylene are melted and the holding time at thetemperature can be changed to obtain a desired ratio of extended tofolded chain crystals and amorphous content.

Irradiation cross-links the high pressure crystallized polyethylene andprovides wear resistance. Irradiation can be done at room temperature orat elevated temperatures below the melting point of polyethylene.Irradiation can be done in air, in vacuum, or in oxygen-freeenvironment, including inert gases such as nitrogen or noble gases.Irradiation is done by using electron-beam, gamma irradiation, or x-rayirradiation.

The adverse oxidative effects of residual free radicals caused byionizing radiation are reduced by diffusing an antioxidant such asu-tocopherol into high pressure crystallized, partially melted andcross-linked polyethylene. The antioxidant prevents oxidation ofirradiated materials. Doping of polyethylene by an antioxidant isperformed as described herein.

The adverse oxidative effects of residual free radicals caused byionizing radiation is reduced by using a blend of polymer and additive,which is also an antioxidant, such as α-tocopherol to high pressurecrystallize and irradiate.

In another aspect, the residual free radicals caused by ionizingradiation are removed by mechanical annealing, where the polyethylene isheated to a temperature below the melting point (less than about 150°C.), preferably 145° C., more preferably at about 148° C. and deformedmechanically to provide mobility for the residual free radicals torecombine and stabilize.

In another aspect, the residual free radicals generated during ionizingradiation is to removed by heating polyethylene to melt. Melting of theirradiated polyethylene is used as part of high-pressure crystallizationsubsequent to irradiation.

A high crystalline polyethylene is made by a process comprisinghigh-pressure crystallization of unirradiated polyethylene, followed byirradiation, and elimination of the free radicals generated during theprocess, with minimum compromise in the crystallinity achieved.

According to one aspect of the invention, polyethylene is pressurized toabove about 10-1800 MPa (for example, at least about 150 MPa, 200 MPa,250 MPa, 300 MPa, 310 MPa, 320 MPa, 380 MPa, 400 MPa, or 450 MPa),preferably at least about 150 MPa, more preferably at least 250 MPa, yetmore preferably to above 320 MPa, heated to either about 180 or about225° C., held at that temperature and that pressure, cooled to roomtemperature, reduced pressure to ambient, and irradiated at roomtemperature. Subsequently, one of the following processes can beemployed in order to improve oxidation resistance of the high pressurecrystallized polyethylene; a) doping the high pressure crystallizedpolyethylene with an antioxidant, such as vitamin E; or b) mechanicallydeforming the high pressure crystallized polyethylene below its meltingpoint followed by annealing near its melting point, essentially applyingany of the CIMA methods, and c) heating to above the melting point,pressurizing to at least about 10-1000 MPa (for example, at least about150 MPa, 200 MPa, 250 MPa, 300 MPa, 310 MPa, 320 MPa, 380 MPa, 400 MPa,or 450 MPa), preferably at least about 150 MPa, more preferably at least250 MPa, yet more preferably above 380 MPa, holding at this temperatureand pressure, cooling to about room temperature, reducing pressure toambient.

A potential draw-back of irradiating a highly crystalline polyethyleneat room temperature can be that the reduced concentration of amorphousphase, where cross-linking primarily takes place, in a polyethylene withincreased crystallinity can also reduce the concentration of crosslinksformed by irradiation. Therefore, it is preferable to irradiatepolyethylene at an elevated temperature where the polymer isapproximately 60% or less crystalline to increase the amorphous content.High pressure crystallized polyethylene exhibits two melting peaks, oneat about 137° C. and the other at above about 140° C. The in second peakis formed during high-pressure crystallization and represents extendedchain crystals (larger ones). The following sequence of events isapplied according to one aspect of the invention: Heated to atemperature below 140° C. to melt some of the smaller crystals and alsocross-linked the regions that contain smaller crystals; irradiated atthis temperature (warm irradiation (WI)), then one of the followingprocesses are employed in order to improve oxidation resistance of thehigh pressure crystallized polyethylene:

a) doping the high-pressure crystallized polyethylene with anantioxidant, such as vitamin E; and

b) melt by heating to above the melting point, then pressurizing to atleast about 10-1000 MPa (for example, at least about 150 MPa, 200 MPa,250 MPa, 300 MPa, 310 MPa, 320 MPa, 380 MPa, 400 MPa, or 450 MPa),preferably at least about 150 MPa, more preferably at least 250 MPa, yetmore preferably above 320 MPa, holding pressure and temperature aboutconstant, cooling to about room temperature, and reducing pressure toambient. The melting step of this process will eliminate the crystals;therefore, the process is followed by high-pressure crystallization toachieve a high level of crystallinity.

In one aspect of the invention, the doping of high pressure crystallizedpolyethylene is carried out by diffusion of an additive, for example,α-tocopherol, such as vitamin E. According to one aspect of theinvention, diffusion of the additive is accelerated by increasing thetemperature and or pressure.

According to another aspect of the invention, an additive is deliveredin various forms, including in a pure form, for example, as pure vitaminE, or dissolved in a solvent.

According to another aspect of the invention, the diffusion rate of anadditive into the polyethylene is increased by increasing theconcentration of the additive solution, for example, a vitamin Esolution.

In accordance with another aspect of the invention, diffusion rate of anantioxidant into the polyethylene is increased by swelling the highpressure crystallized polyethylene in a supercritical fluid, forexample, in a supercritical CO₂, i.e., the temperature being above thesupercritical temperature, which is 31.3° C., and the pressure beingabove the supercritical pressure, which is 73.8 bar.

Doping in the consolidated state also allows one to achieve a gradientof antioxidant in consolidated polymeric material. One can dope acertain thickness surface layer where the oxidation of the polymericmaterial in a medical device is of concern in terms of wear. This can beachieved by simply dipping or soaking finished devices, for example, afinished medical implant, for example, in pure vitamin F or in asolution of vitamin E at a given temperature and for a given amount oftime.

According to the methods described herein, an antioxidant, for example,vitamin E, is doped into the high-pressure crystallized polymericmaterial before, during, or after irradiation.

It may be possible that the doped antioxidant can leach out of thepolymeric material used in fabrication of medical implants or medicaldevices either during storage prior to use or during in vivo service.For a permanent medical device, the in vivo duration can be as long asthe remaining life of the patient, which is the length of time betweenimplantation of the device and the death of the patient, for example,1-120 years. If leaching out of the antioxidant is an issue, theirradiation of the medical implant or medical device or irradiation ofany portion thereof can be carried out after doping the antioxidant.This can ensure cross-linking of the antioxidant to the host polymerthrough covalent bonds and thereby minimize or prevent loss ofantioxidant from the medical implant or the device.

According to another aspect of the invention, antioxidant-dopedpolymeric material or an antioxidant-doped medical implant can be washedin an industrial washer with detergent before packaging andsterilization. An industrial washer, for example, a washer/dryer such asa HAMO T-21 or a washer/disinfectant/dryer such as a HAMO M-100 (HAMOAG, Pieterlen, Switzerland) can be used.

According to another aspect of the invention, antioxidant-dopedpolymeric material; or an antioxidant-doped medical implant is soaked ina solvent such as ethanol before packaging and sterilization. A solvent,in which the antioxidant dissolves, is chosen so that the cleaningenvironment can provide a conducive environment for removing the inantioxidant from the polymeric material. This decreases the possibilityof antioxidant leaching from the antioxidant-doped polymeric material.The solvent can be at room temperature or at elevated temperatures,under ambient pressure or under elevated pressures, still or stirred.The time for the antioxidant-doped polymeric material or medical implantin contact with the solvent can range from about an hour to at least aslong as the time that the doping was done, preferably less than 16hours.

According to another aspect of the invention, polymeric material, forexample, resin powder, flakes, particles, or a mixture thereof, is mixedwith an additive and then the mixture is consolidated. The consolidatedadditive-doped polymeric material (blend) is machined to use as acomponent in a medical implant or as a medical device,

According to another aspect of the invention, high-pressure crystallizedpolymeric material, for example, high pressure crystallized resinpowder, molded sheet, blown films, tubes, balloons, flakes, particles,or a mixture thereof, is doped with an additive, for example, vitamin Ein the form of α-Tocopherol, by diffusion. High pressure crystallizedpolymeric material, for example, high pressure crystallized UHMWPE issoaked in 100% vitamin E or in a solution of α-Tocopherol in an alcohol,for example, ethanol or isopropanol. A solution of α-Tocopherol, about50% by weight in ethanol is used to diffuse in to UHMWPE in contact witha supercritical fluid, such as CO².

The invention also relates to the following processing steps tofabricate medical devices made out of highly cross-linked polyethyleneand containing metallic pieces such as bipolar hip replacements, tibialknee inserts with reinforcing metallic and polyethylene posts,intervertebral disc systems, and for any implant that contains a surfacethat cannot be readily sterilized by a gas sterilization method.

According to one aspect of the invention, the high pressure crystallizedpolyethylene component of a medical implant is in close contact withanother material (that is a non-modular implant), such as a metallicmesh or back, a non-metallic mesh or back, a tibial tray, a patellatray, or an acetabular shell, wherein the polyethylene, such as resinpowder, flakes and particles are directly compression molded to thesecounter faces. For example, a polyethylene tibial insert is manufacturedby compression molding of polyethylene resin powder to a tibial tray, toa metallic mesh or back or to a non-metallic mesh or back. In the lattercase, the mesh is shaped to serve as a fixation interface with the bone,through either bony in-growth or the use of an adhesive, such aspolymethylmethacrylate (PMMA) bone cement. These shapes are of variousforms including, acetabular liner, tibial tray for total orunicompartmental knee implants, patella tray, and glenoid component,ankle, elbow or finger component. Another aspect of the inventionrelates to mechanical interlocking of the molded polyethylene with theother piece(s), for example, a metallic or a non-metallic piece, thatmakes up part of the implant. The consolidated polyethylene withmetallic piece is then high-pressure crystallized (HPC) to achieve ahighly crystalline polyethylene. The HPC can is carried out by eitherfirst heating or pressurizing the non-modular implant.

The interface geometry is crucial in that polyethylene assumes thegeometry as its consolidated shape. Polyethylene has a remarkableproperty of ‘shape memory’ due to its very high molecular weight thatresults in a high density of physical entanglements. Followingconsolidation, plastic deformation introduces a permanent shape change,which attains a preferred high entropy shape when melted. This recoveryof the original consolidated shape is due to the ‘shape memory’, whichis achieved when the polyethylene is consolidated. Because of this shapememory, the mechanical interlock will remain intact during and after thehigh-pressure crystallization of the non-modular implant.

Another aspect of the invention provides that following thehigh-pressure crystallization of the polyethylene that was molded to thecounterface with the mechanical interlock, the hybrid component isirradiated using ionizing radiation to a desired dose level, forexample, about 25 kGy to about 1000 kGy, preferably between about 50 kGyand about 150 kGy. Another aspect of the invention discloses that theirradiation step generates residual free radicals and therefore, amelting step is introduced thereafter to quench the residual freeradicals followed by another step of high-pressure crystallization.Since the polyethylene is first consolidated into the shape of theinterface, thereby setting a ‘shape memory’ of the polymer, thepolyethylene does not separate from the counterface during melting andsubsequent high-pressure crystallization step.

In another aspect of the invention, there are provided methods ofcross-linking polyethylene, to create a polyethylene-based medicaldevice, wherein the device is immersed in an oxidation-resistant mediumsuch as inert gas or inert fluid, wherein the medium is heated to abovethe melting point of the irradiated highly crystalline polyethylene, forexample, high pressure crystallized UHMWPE (above about 140° C.) toeliminate the crystalline matter and to allow therecombination/elimination of the residual free radicals. Because theshape memory of the compression molded polymer is set at themechanically interlocked interface and that memory is strengthened bythe cross-linking step, there is no significant separation at theinterface between the polyethylene and the counterface.

Another aspect of the invention provides that following the above stepsof free radical elimination, the interface between the metal and thepolymer become sterile due to the high irradiation dose level usedduring irradiation. When there is substantial oxidation on the outsidesurface of the HPC-polyethylene induced during the free radicalelimination step or irradiation step, the device surface is furthermachined to remove the oxidized surface layer. In another aspect, theinvention provides that in the case of a post-melting machining of animplant, the melting step is carried out in the presence of an inertgas.

Another aspect of the invention includes methods of sterilization of thefabricated device, wherein the device is further sterilized withethylene oxide, gas plasma, or the other gases, when the interface issterile but the rest of the component is not.

Heating and Pressurization Via the Melt Phase:

The hexagonal phase of polyethylene is achieved by going through themelt phase or by going through the orthorhombic phase (see FIG. 1A). Thefirst is achieved by using heating and pressurization methods such thatimmediately before the hexagonal phase transition is encountered, thesample is in the melt phase.

In one embodiment, the sample is first heated to a temperature above themelting temperature of polyethylene under an ambient pressure (about135° C.) or to above the melting temperature of polyethylene at about40,000 psi, subsequently pressurized so that the melt to hexagonal phasetransition is achieved. An example of the heating and pressurizationcycle for this embodiment is shown in FIG. 1B.

In another embodiment, the sample is heated and pressurized at the sametime so that first the transition from the orthorhombic phase into themelt phase is achieved, then the transition from the melt, phase intothe hexagonal phase is achieved (see FIG. 1C, for example).

In another embodiment, the sample is pressurized first to a pressurebelow the triple point of the polymer, subsequently heated such that themelt phase transition is achieved at this pressure, subsequently furtherpressurized to achieve the melt to hexagonal phase transition (see FIG.1D, for example).

In another embodiment, the sample is heated and pressurized in astepwise manner in the orthorhombic or melt phases as long as thetransition to the hexagonal phase is achieved from the melt phase (seeFIG. 1E, for example).

In another embodiment, the sample is heated above the desired highpressure crystallization temperature, then subsequently cooled whilepressurizing such that the transition to the hexagonal phase is achievedfrom the melt phase (see FIG. 1F, for example).

In another embodiment, heating and pressurization is carried out suchthat the sample is heated and pressurized through the hexagonal phaseinto the melt phase, then is subsequently cooled and depressurized tocrystallize in the hexagonal phase (see FIG. 1G, for example).

Heating and Pressurization Via the Orthorhombic Phase:

Alternatively, to enter the hexagonal phase from the melt phase, thesample is crystallized in the hexagonal phase by going through theorthorhombic phase (see FIG. 1A, for example). In one embodiment, thesample is pressurized to above the triple point, and subsequently heatedto achieve the orthorhombic to hexagonal phase transition (see FIG. 1H,for example).

In another embodiment, pressurization and heating is done at the sametime without encountering the melt phase and such that the hexagonalphase transition is achieved from the orthorhombic phase (see FIG. 1Iand 1J, for example).

In another embodiment, the sample is first heated to a temperature belowthe melting temperature of the polymer at ambient pressure, subsequentlyheated and pressurized without encountering, the melt phase such thatthe hexagonal phase transition is achieved from the orthorhombic phase(see FIG. 1K, for example).

In another embodiment, heating and pressurization from the orthorhombicphase at ambient pressure and temperature is done stepwise at differentrates to achieve the orthorhombic to hexagonal phase transition (seeFIG. 1L, for example).

In another embodiment, the sample is first heated to a temperature belowthe melting point of the polymer at ambient pressure, cooled whilepressurizing, heated further, and this process can be repeated until theorthorhombic to hexagonal phase transition is achieved (see FIG. 1M, forexample).

In yet another embodiment, the sample is first pressurized to a pressureabove the desired high pressure crystallization pressure in theorthorhombic phase, then subsequently depressurized while heating toachieve the orthorhombic to hexagonal phase transition (see FIG. 1N, forexample).

Cooling and Depressurization:

Once the hexagonal phase transition has been achieved and the polymerhas stayed in the hexagonal phase for a desired period of time thencooling and depressurization is achieved in different ways. In order topreserve the crystals formed in the hexagonal phase, the sample has tobe cooled down in a way that the melt transition is not fullyencountered. The following embodiments describe several methods asexamples to how this is achieved.

In one embodiment, the sample is cooled down under constant pressure toabout room temperature and subsequently the pressure is released. Inthis manner, first the hexagonal to orthorhombic phase transition isachieved and then the sample is in depressurized in the orthorhombicphase (see FIG. 10, for example). In this method, what is meant byconstant pressure is pressure within about 5000 psi of the originalvalue.

In another embodiment, the sample is cooled down and depressurized atthe same time in a non-linear fashion without encountering the meltphase (sec FIG. 1P, for example). The pressure is released at the sametime cooling the sample down to below the melting temperature of thepolymer at ambient pressure.

Alternatively, the sample is cooled and depressurized in a stepwisefashion without encountering the melt phase (see FIGS. 1Q-1U, forexample). In one embodiment, the sample is cooled to and maintained at atemperature above the melting point of the polymer at ambient pressurewhile depressurizing partially (see FIG. 1R, for example) or cooled toand maintained at a temperature below the melting point of the polymerat ambient pressure while depressurizing partially (see FIG. 1S, forexample). Subsequently, the sample is further cooled to about roomtemperature and the rest of the pressure is released.

In another embodiment, the polymer sample is cooled down under constantpressure to about a temperature below the melting point of the polymerat ambient pressure and subsequently the pressure is released (see FIG.1T, for example). In this manner, first the hexagonal to orthorhombicphase transition is achieved and then the sample is depressurized in theorthorhombic phase. In this method, what is meant by constant pressureis pressure within about 5000 psi of the original value.

According to one aspect of the invention, the cooling rate is 0.001°C./min to 500° C./min, more preferably about 0.1° C./min to 5° C./min,more preferably about 1° ”C./min. In another aspect of the invention,the depressurization is about 100 psi/min to 500,000 psi/min, morepreferably about 1000 psi/min to 45000 psi/min, more preferably about10000 psi/min. In another aspect of the invention, the holding time atany of the constant pressure or temperature steps is from 0.1 minute to500 hours, more preferably about 1 minute to 600 minutes, morepreferably about 1 hour to 8 hours, more preferably about 4 hours. Theeffect of holding time on the sample depends on the sample size. If theentire sample does not come to same temperature, there can be gradientsin the polymer. Gradients are desirable for certain applications.

Alternatively, in another aspect of the invention, the sample is cooleddown to below the melting temperature of the polymer at ambientpressure, then pressurized further, maintained at this pressure andtemperature, then the pressure is released, then the sample is cooleddown to about room temperature (See FIG. 1U, for example).

In one embodiment, the sample is cooled down and depressurized overall,via cooling, heating and depressurization and pressurization steps (SeeFIGS. 1V and 1W, for example).

In another embodiment, the sample is taken into the melt transitionwhile cooling and depressurization. Depending on the time spent in themelt phase and the sample size, part or all of the extended chaincrystals formed in the hexagonal phase is melted and if the sample issubsequently immediately cooled down and depressurized to about roomtemperature and ambient pressure, the melted crystals are recrystallizedas folded chain crystals.

Irradiation of a Finished Product Made of a Blend of UHMWPE with anAdditive followed by High-Pressure Crystallization:

According to one aspect of the invention, a finished product, forexample, an article, a medical device, or a medical prosthesis and thelike, is irradiated and then high pressure crystallized as follows:Polymeric material, for example, resin powder, flakes, particles, or amixture thereof; is mixed/blended with an additive, for example, anantioxidant, preferably vitamin E (preferably less than about 10%, morepreferably less than 5%, more preferably less than 0.3%, and yet morepreferably 0.1% vitamin E) and then form an article or a medial deviceby:

-   -   a. Consolidating the blend, preferably by adding a step to        anneal the consolidated blend to remove thermal stresses; and    -   b. Machining the blend to form a finished product; or    -   c. Direct compression molding the blend to form a finished        product.

The finished product is irradiated to at least 1 kGy, preferably about25 kGy to about 1000 kGy or more, more preferably a dose of about 25,50, 75, 100, 125, 150, 175, or 200 kGy by gamma, e-beam, or x-ray.

The irradiated finished product is high pressure crystallized by either:

-   -   a. Heating to a temperature above the melting point of the        irradiated polyethylene under an ambient pressure, pressurizing        to at least about 10-1000 MPa (for example, at least about 150        MPa, 200 MPa, 250 MPa, 300 MPa, 310 MPa, 320 MPa, 380 MPa, 400        MPa, or 450 MPa), preferably at least about 150 MPa, more        preferably at least about 250 MPa, cooling to about room        temperature while under pressure, and releasing the pressure; or    -   b. Pressurizing to at least about 10-1000 MPa (for example, at        least about 150 MPa, 200 MPa, 250 MPa, 300 MPa, 310 MPa, 320        MPa, 380 MPa, 400 MPa, or 450 MPa), preferably at least about        150 MPa, more preferably at least about 250 MPa, heating to a        temperature above the melting point of the irradiated        polyethylene under an ambient pressure, cooling to about room        temperature, and releasing pressure.

The high pressure crystallized finished product can be packaged andsterilized.

Irradiation, Melting, and Machining of a Finished Product Prior toHigh-Pressure Crystallization:

According to another aspect of the invention, a finished product, forexample, an article, a medical device or a medical prosthesis and thelike, is irradiated, melted, machined, and then high pressurecrystallized as follows:

Polymeric material is irradiated, melted, and machined to form afinished product, for example, an article, a medical device, or amedical prosthesis and the like.

The finished product is high pressure crystallized by either:

-   -   a. Heating to a temperature above the melting point of the        irradiated polyethylene under an ambient pressure, pressurizing        to at least about 10-1000 MPa (for example, at least about 150        MPa, 200 MPa, 250 MPa, 300 MPa, 310 MPa, 320 MPa, 380 MPa, 400        MPa, or 450 MPa), preferably at least about 150 MPa, more        preferably at least about 250 MPa, cooling to about room        temperature while under pressure, and releasing the pressure; or    -   b. Pressurizing to at least about 10-1000 MPa (for example, at        least about 150 MPa, 200 MPa, 250 MPa, 300 MPa, 310 MPa, 320        MPa, 380 MPa, 400 MPa, or 450 MPa), preferably at least about        150 MPa, more preferably at least about 250 MPa, heating to a        temperature above the melting point of the irradiated        polyethylene under an ambient pressure, cooling to about room        temperature, and releasing pressure.

The high pressure crystallized finished product can be packaged andsterilized

Irradiation and Machining of a Finished Product Prior to High-PressureCrystallization:

According to another aspect of the invention, a finished product, forexample, an article, a medical device or a medical prosthesis and thelike, is irradiated, machined, and then high pressure crystallized asfollows:

Polymeric material is irradiated and machined to form a finishedproduct, for example, an article, a medical device, or a medicalprosthesis and the like.

The finished product is high pressure crystallized by either:

-   -   a. Heating to a temperature above the melting point of the        irradiated polyethylene under an ambient pressure, pressurizing        to at least about 10-1000 MPa (for example, at least about 150        MPa, 200 MPa, 250 MPa, 300 MPa, 310 MPa, 320 MPa, 380 MPa, 400        MPa, or 450 MPa), preferably at least about 150 MPa, more        preferably at least about 250 MPa, cooling to about room        temperature while under pressure, and releasing the pressure; or    -   b. Pressurizing to at least about 10-1000 MPa (for example, at        least about 150 MPa, 200 MPa, 250 MPa, 300 MPa, 310 MPa, 320        MPa, 380 MPa, 400 MPa, or 450 MPa), preferably at least about        150 MPa, more preferably at least about 250 MPa, heating to a        temperature above the melting point of the irradiated        polyethylene under an ambient pressure, cooling to about room        temperature, and releasing pressure.

The high pressure crystallized finished product can be packaged andsterilized.

Warm Irradiation, Melting, and Machining of a Finished Product Prior toHigh-Pressure Crystallization;

According to another aspect of the invention, a finished product, forexample, an in article, a medical device or a medical prosthesis and thelike, is warm irradiated, melted, machined, and then high pressurecrystallized as follows:

Polymeric material is warm irradiated to above room temperature, such asa temperature above about 80° C. and below the melting point of thepolymeric material. The warm irradiated polymeric material is melted,and machined to form a finished product, for example, an article, amedical device, or a medical prosthesis and the like.

The finished product is high pressure crystallized by either:

-   -   a. Heating to a temperature above the melting point of the        irradiated polyethylene under an ambient pressure, pressurizing        to at least about 10-1000 MPa (for example, at least about 150        MPa, 200 MPa, 250 MPa, 300 MPa, 310 MPa, 320 MPa, 380 MPa, 400        MPa, or 450 MPa), preferably at least about 150 MPa, more        preferably at least about 250 MPa, cooling to about room        temperature while under pressure, and releasing the pressure; or    -   b. Pressurizing to at least about 10-1000 MPa (for example, at        least about 150 MPa, 200 MPa, 250 MPa, 300 MPa, 310 MPa, 320        MPa, 380 MPa, 400 MPa, or 450 MPa), preferably at least about        150 MPa, more preferably at least about 250 MPa, heating to a        temperature above the melting point of the irradiated        polyethylene under an ambient pressure, cooling to about room        temperature, and releasing pressure.

The high pressure crystallized finished product can be packaged andsterilized.

Warm Irradiation and Machining of a Finished Product Prior toHigh-Pressure Crystallization:

According to another aspect of the invention, a finished product, forexample, an article, a medical device or a medical prosthesis and thelike, is warm irradiated, machined, and then high pressure crystallizedas follows:

Polymeric material is warn irradiated to above room temperature, such asa temperature above about 80° C. and below the melting point of thepolymeric material and machined to form a finished product, for example,an article, a medical device, or a medical prosthesis and the like.

The finished product is high pressure crystallized by either:

-   -   a. Heating to a temperature above the melting point of the        irradiated polyethylene under an ambient pressure, pressurizing        to at least about 10-1000 MPa (for example, at least about 150        MPa, 200 MPa, 250 MPa, 300 MPa, 310 MPa, 320 MPa, 380 MPa, 400        MPa, or 450 MPa), preferably at least about 150 MPa, more        preferably at least about 250 MPa, cooling to about room        temperature while under pressure, and releasing the pressure; or    -   b. Pressurizing to at least about 10-1000 MPa (for example, at        least about 150 MPa, 200 MPa, 250 MPa, 300 MPa, 310 MPa, 320        MPa, 380 MPa, 400 MPa, or 450 MPa), preferably at least about        150 MPa, more preferably at least about 250 MPa, heating to a        temperature above the melting point of the irradiated        polyethylene under an ambient pressure, cooling to about room        temperature, and releasing pressure.

The high pressure crystallized finished product can be packaged andsterilized.

Cold Irradiation and Mechanically Annealing (CIMA) and Machining of aFinished Product Prior to High-Pressure Crystallization:

According to another aspect of the invention, a finished product, forexample, an article, a medical device or a medical prosthesis and thelike, is irradiated by a CIMA method, machined, and then high pressurecrystallized, as follows:

Polymeric material is irradiated and mechanically deformed at anelevated temperature, such as above 90° C. and below 140° C. anddeformed under pressure until cooled down to room temperature, annealedabove room temperature, such as at above 90° C. and below 140° C. torecover the deformed state, and machined to form a finished product, forexample, an article, a medical device, or a medical prosthesis and thelike.

The finished product is high pressure crystallized by either:

-   -   a. Heating to a temperature above the melting point of the        irradiated polyethylene under an ambient pressure, pressurizing        to at least about 10-1000 MPa (for example, at least about 150        MPa, 200 MPa, 250 MPa, 300 MPa, 310 MPa, 320 MPa, 380 MPa, 400        MPa, or 450 MPa), preferably at least about 150 MPa, more        preferably at least about 250 MPa, cooling to about room        temperature while under pressure, and releasing the pressure; or    -   b. Pressurizing to at least about 10-1000 MPa (for example, at        least about 150 MPa, 200 MPa, 250 MPa, 300 MPa, 310 MPa, 320        MPa, 380 MPa, 400 MPa, or 450 MPa), preferably at least about        150 MPa, more preferably at least about 250 MPa, heating to a        temperature above the melting point of the irradiated        polyethylene under an ambient pressure, cooling to about room        temperature, and releasing pressure.

The high pressure crystallized finished product can be packaged andsterilized.

DEFINITIONS

“High pressure crystallized” (HPC) refers to a state of a polymericmaterial that has undergone high-pressure crystallization process,according to the invention, as described herein.

“High-pressure crystallization” refers to a method of making highpressure crystallized polyethylene, according to the invention, asdescribed herein.

The term “highly crystalline” or “high crystallinity” refers to a stateof a material of at least about 51% crystallinity.

An “additive” refers to what is known in the art as additional componentother than the polymeric material. An “additive” can be, for example, anucleating agent, an antioxidant, a lipid, a low molecular weightpolyethylene.

“Antioxidant” refers to what is known in the art as (see, for example,WO 01/80778, U.S. Pat. No. 6,448,315). Alpha- and delta-tocopherol;propyl, octyl, or dedocyl gallates; lactic, citric, and tartaric acidsand their salts; orthophosphates, tocopherol acetate. Preferably vitaminE. An “additive” includes antioxidants and the like.

“Supercritical fluid” refers to what is known in the art, for example,supercritical propane, acetylene, carbon dioxide (CO₂). In thisconnection the critical temperature is that temperature above which agas cannot be liquefied by pressure alone. The pressure under which asubstance may exist as a gas in equilibrium with the liquid at thecritical temperature is the critical pressure. Supercritical fluidcondition generally means that the fluid is subjected to such atemperature and such a pressure that a supercritical fluid and thereby asupercritical fluid mixture is obtained, the temperature being above thesupercritical temperature, which for CO₂ is 31.3° C., and the pressurebeing above the supercritical pressure, which for CO₂ is 73.8 bar. Morespecifically, supercritical condition refers to a condition of amixture, for example, UHMWPE, with an antioxidant, at an elevatedtemperature and pressure, when a supercritical fluid mixture is formedand then evaporate CO₂ from the mixture, UHMWPE doped with anantioxidant is obtained (see, for example, U.S. Pat. No. 6,448,315 andWO 02/26464)

The term “compression molding” as referred herein related generally towhat is known in the art and specifically relates to high temperaturemolding polymeric material wherein polymeric material is in any physicalstate, including powder form, is compressed into a slab form or mold ofa medical implant, for example, a tibial insert, an acetabular liner, aglenoid liner, a patella, or an unicompartmental insert.

The term “direct compression molding” as referred herein relatedgenerally to what is known in the art and specifically relates tomolding applicable in polyethylene-based devices, for example, medicalimplants wherein polyethylene in any physical state, including powderform, is compressed to solid support, for example, a metallic back,metallic mesh, or metal surface containing grooves, undercuts, orcutouts. The compression molding also includes high temperaturecompression molding of polyethylene at various states, including resinpowder, flakes and particles, to make a component of a medical implant,for example, a tibial insert, an acetabular liner, a glenoid liner, apatella, or an unicompartmental insert, to the counterface.

The term “mechanically interlocked” refers generally to interlocking ofpolyethylene and the counterface, that are produced by various methods,including compression molding, heat and irradiation, thereby forming aninterlocking interface, resulting into a ‘shape memory’ of theinterlocked polyethylene. Components of a device having such aninterlocking interface can be referred to as a “hybrid material”.Medical implants having such a hybrid material, contain a substantiallysterile interface.

The term “substantially sterile” refers to a condition of an object, forexample, an interface or a hybrid material or a medical implantcontaining interface(s), wherein the interface is sufficiently sterileto be medically acceptable, i.e., will not cause an infection or requirerevision surgery.

“Metallic mesh” refers to a porous metallic surface of various poresizes, for example, 0.1-3 mm. The porous surface can be obtained throughseveral different methods, for example, sintering of metallic powderwith a binder that is subsequently removed to leave behind a poroussurface; sintering of short metallic fibers of diameter 0.1-3 mm; orsintering of different size metallic meshes on top of each other toprovide an open continuous pore structure.

“Bone cement” refers to what is known in the art as an adhesive used inbonding medical devices to bone. Typically, bone cement is made out ofpolymethylmethacrylate (PMMA).

“High temperature compression molding” refers to the compression moldingof polyethylene in any form, for example, resin powder, flakes orparticles, to impart new geometry under pressure and temperature. Duringthe high temperature (above the melting point of polyethylene)compression molding, polyethylene is heated to above its melting point,pressurized into a mold of desired shape and allowed to cool down underpressure to maintain a desired shape.

“Shape memory” refers to what is known in the art as the property ofpolyethylene, for example, an UHMWPE, that attains a preferred highentropy shape when melted. The preferred high entropy shape is achievedwhen the resin powder is consolidated through compression molding.

The phrase “substantially no detectable residual free radicals” refersto a state of a polyethylene component, wherein enough free radicals areeliminated to avoid oxidative degradation, which can be evaluated byelectron spin resonance (ESR). The phrase to “detectable residual freeradicals” refers to the lowest level of free radicals detectable by ESR.The lowest level of free radicals detectable with state-of-the-artinstruments is about 10¹⁴ spins/gram and thus the term “detectable”refers to a detection limit of 10¹⁴ spins/gram by ESR.

The terms “about” or “approximately” in the context of numerical valuesand ranges refers to values or ranges that approximate or are close tothe recited values or ranges such that the invention can perform asintended, such as having a desired degree of crystallinity orcross-linking and/or a desired lack of free radicals, as is apparent tothe skilled person from the teachings contained herein. This is due, atleast in part, to the varying properties of polymer compositions. Thusthese terms encompass values beyond those resulting from systematicerror.

Polymeric Material: Ultra-high molecular weight polyethylene (UHMWPE)refers to linear non-branched chains of ethylene having molecularweights in excess of about 500,000, preferably above about 1,000,000,and more preferably above about 2,000,000. Often the molecular weightscan reach about 8,000,000 or more. By initial average molecular weightis meant the average molecular weight of the UHMWPE starting material,prior to any irradiation. See U.S. Pat. No. 5,879,400, PCT/US99/16070,filed on Jul. 16, 1999, PCT/US97/02220. filed Feb. 11, 1997, and USPatent publication 20030149125 (U.S. application Ser. No. 10/252,582),filed Sep. 24, 2002.

The products and processes of this invention also apply to various typesof polymeric materials, for example, any polyolefin, includinghigh-density-polyethylene, low-density-polyethylene,linear-low-density-polyethylene, ultra-high molecular weightpolyethylene (UHMWPE), or mixtures thereof Polymeric materials, as usedherein, also applies to polyethylene of various forms, for example,resin powder, flakes, particles, powder, or a mixture thereof, or aconsolidated form derived from any of the above.

The term “additive” refers to any material that can be added to a basepolymer in less than 50 v/v %. This material can be organic or inorganicmaterial with a molecular weight less than that of the base polymer. Anadditive can impart different properties to the polymeric material, forexample, it can be a plasticizing agent, a nucleating agent, or anantioxidant.

“Blending” generally refers to mixing of a polyolefin in itspre-consolidated form with an additive. If both constituents are solid,blending can be done by using a third component such as a liquid tomediate the mixing of the two components, after which the liquid isremoved by evaporating. If the additive is liquid, for exampleα-tocopherol, then the solid can be mixed with large quantities ofliquid, then diluted down to desired concentrations with the solidpolymer to obtain uniformity in the blend. In the case where an additiveis also an antioxidant, for example vitamin E, or α-tocopherol, thenblended polymeric material is also antioxidant-doped. Polymericmaterial, as used herein, also applies to blends of a polyolefin and aplasticizing agent, for example a blend of UHMWPE resin powder blendedwith a-tocopherol and consolidated. Polymeric material, as used herein,also applies to blends of an additive, a polyolefin and a plasticizingagent, for example UHMWPE soaked in u-tocopherol.

“Plasticizing agent” refers to a what is known in the art, a materialwith a molecular weight less than that of the base polymer, for exampleα-tocopherol in polyethylene or low molecular weight polybutadiene inpolyethylene, in both cases polyethylene being the base polymer. Theplasticizing agent is typically added to the base polymer in less thanabout 20 weight percent. The plasticizing agent increases flexibilityand softens the polymeric material.

The term “plasticization” or “plasticizing” refers to the propertiesthat a plasticizing agent imparts on the polymeric material into whichit has been added. There properties may include but are not limited toincreased elongation at break, reduced stiffness, and increasedductility.

A “nucleating agent” refers to an additive known in the art, an organicor inorganic material with a molecular weight less than that of the basepolymer, which increases the rate of crystallization in the polymericmaterial. Typically, organocarboxylic acid salts, for example calciumcarbonate, are good nucleation agents for polyolefins. Also, nucleatingagents are typically used in small concentrations such as 0.5 wt %.

Doping: Doping refers to a process well known in the art (see, forexample, U.S. Pat. Nos. 6,448,315 and 5,827,904). In this connection,doping generally refers to contacting a polymeric material with anantioxidant under certain conditions, as set forth herein, for example,doping UHMWPE with an antioxidant under supercritical conditions.“Doping” also refers to introducing a second component into the base ispolymeric material in quantities less than 50 v/v %. More specifically,doping refers to introducing an antioxidant into a polymeric material,most often by diffusion of the antioxidant from a surrounding media intothe polymeric material. A polymeric material treated in such a way istermed as “antioxidant-doped” polymeric material. However, the processof doping an antioxidant into a polymeric material is not limited to thediffusion process. The polymeric material can be ‘doped’; however, byother additives as well, such as a plasticizing agent, in which case thepolymeric material treated in such a way may be termed as ‘plasticizingagent-doped’.

More specifically, for example, HPC polymeric material can be doped withan antioxidant by soaking the material in a solution of the antioxidant.This allows the antioxidant to diffuse into the polymer. For instance,the material can be soaked in 100% antioxidant. The material also can besoaked in an antioxidant solution where a carrier solvent can be used todilute the antioxidant concentration. To increase the depth of diffusionof the antioxidant, the material can be doped for longer durations, athigher temperatures, at higher pressures, and/or in presence of asupercritical fluid.

The doping process can involve soaking of a polymeric material, medicalimplant or device with an antioxidant, such as vitamin E, for about anhour up to several days, preferably for about one hour to 24 hours, morepreferably for one hour to 16 hours. The antioxidant can be heated toroom temperature or up to about 160° C. and the doping can be carriedout at room temperature or up to about 160° C. Preferably, theantioxidant can be heated to 100° C. and the doping is carried out at100° C.

To further increase the uniformity of antioxidant in the base polymericmaterial, the doped polymeric material is annealed below or above themelt under ambient or high pressure. The annealing is preferably forabout an hour up to several days, more preferably in for about one hourto 24 hours, most preferably for one hour to 16 hours. The dopedpolymeric material is heated to room temperature or up to about 60° C.and the annealing is carried out at room temperature or up to about 160°C. Preferably, the doped polymeric material is heated to about 120° C.and the annealing is carried out at about 120° C.

The term “conventional UHMWPE” refers to commercially availablepolyethylene of molecular weights greater than about 500,000.Preferably, the UHMWPE starting material has an average molecular weightof greater than about 2 million.

By “initial average molecular weight” is meant the average molecularweight of the UHMWPE starting material, prior to any irradiation.

Cross-linking Polymeric Material: Polymeric Materials, for example,UHMWPE can be cross-linked by a variety of approaches, including thoseemploying cross-linking chemicals (such as peroxides and/or silane)and/or irradiation. Preferred approaches for cross-linking employirradiation. Cross-linked UHMWPE can be obtained according to theteachings of U.S. Pat. 5,879,400, PCT/US99/16070, filed on Jul. 16,1999, PCT/US97/02220, filed Feb. 11, 1997, US Patent Publication20030149125 (U.S. application Ser. No. 10/252,582), filed Sep. 24, 2002,and U.S. Pat. No. 6,641,617, the entirety of which are herebyincorporated by reference.

Consolidated Polymeric Material: Consolidated polymeric material refersto a solid, consolidated bar stock, solid material machined from stock,or semi-solid form of polymeric material derived from any forms asdescribed herein, for example, resin powder, flakes, particles, or amixture thereof, that ran be consolidated. The consolidated polymericmaterial also can be in the form of a slab, block, solid bar stock,machined component, film, tube, balloon, pre-form, implant, or finishedmedical device.

By “crystallinity” is meant the fraction of the polymer that iscrystalline. The crystallinity is calculated by knowing the weight ofthe sample (weight in grams), the heat absorbed by the sample in melting(E, in J/g) and the heat of melting of polyethylene crystals (ΔH=291J/g), and using the following equation:

% Crystallinity=E/w·ΔH

By tensile “elastic modulus” is meant the ratio of the nominal stress tocorresponding strain for strains as determined using the standard testASTM 638 M III and the like or their successors.

The term “non-permanent device” refers to what is known in the art as adevice that is intended for implantation in the body for a period oftime shorter than several months. Some non-permanent devices could be inthe body for a few seconds to several minutes, while other may beimplanted for days, weeks, or up to several months. Non-permanentdevices include catheters, tubing, intravenous tubing, and sutures, forexample.

“Permanent device” refers to what is known in the art that is intendedfor implantation in the body for a period longer than several months.Permanent devices include medical devices, for example, acetabularliner, shoulder glenoid, patellar component, finger joint component,ankle joint component, elbow joint component, wrist joint component, toejoint component, bipolar hip replacements, tibial knee insert, tibialknee inserts with reinforcing metallic and polyethylene posts,intervertebral discs, sutures, tendons, heart valves, stents, andvascular grails.

“Pharmaceutical compound”, as described herein, refers to a drug in theform of a powder, suspension, emulsion, particle, film, cake, or moldedform. The drug can be free-standing or incorporated as a component of amedical device.

The term “pressure chamber” refers to a vessel or a chamber in which theinterior pressure can be raised to levels above atmospheric pressure.

The term “packaging” refers to the container or containers in which amedical device is packaged and/or shipped. Packaging can include severallevels of materials, including bags, blister packs, heat-shrinkpackaging, boxes, ampoules, bottles, tubes, trays, or the like or acombination thereof A single component may be shipped in severalindividual types of package, for example, the component can be placed ina bag, which in turn is placed in a tray, which in turn is placed in abox. The whole assembly can be sterilized and shipped. The packagingmaterials include, but not limited to, vegetable parchments, multi-layerpolyethylene. Nylon 6, polyethylene terephthalate (PET), and polyvinylchloride-vinyl acetate copolymer films, polypropylene, polystyrene, andethylene vinyl acetate (EVA) copolymers.

The term “heat-shrinkable packaging” refers to plastic films, bags, ortubes that have a high degree of orientation in them. Upon applicationof heat, the packaging shrinks down as the oriented chains retract,often wrapping tightly around the medical device.

“Melt transition temperature” refers to the lowest temperature at whichall the crystalline domains in a material disappear.

“Melting point” refers to the peak melting temperature measured by adifferential scanning calorimeter at a heating rate of 10° C. per minutewhen heating from 20° C. to 220° C.

Medical implants containing factory-assembled pieces that are in closecontact with the polyethylene form interfaces. In most cases, theinterfaces are not readily accessible to EtO gas or the GP during a gassterilization process.

Irradiation: In one aspect of the invention, the type of radiation,preferably ionizing, is used. According to another aspect of theinvention, a dose of ionizing radiation ranging from about 25 kGy toabout 1000 kGy is used. The radiation dose can be about 50 kGy, about 65kGy, about 75 kGy, about 100 kGy, about 200 kGy, about 300 kGy, about400 kGy, about 500 kGy, about 600 kGy, about 700 kGy, about 800 kGy,about 900 kGy, or about 1000 kGy, or above 1000 kGy, or any integer orfractional value thereabout or therebetween. Preferably, the radiationdose can be between about 50 kGy and about 200 kGy. These types ofradiation, including x-ray, gamma and/or electron beam, kills orinactivates bacteria, viruses, or other microbial agents potentiallycontaminating medical implants, including the interfaces, therebyachieving product sterility. The irradiation, which may be electron orgamma irradiation, in accordance with the present invention can becarried out in air atmosphere containing oxygen, wherein the oxygenconcentration in the atmosphere is at least 1%, 2%, 4%, or up to about22%, or any integer or fractional value thereabout or therebetween. Inanother aspect, the irradiation can be carried out in an inertatmosphere, wherein the atmosphere contains gas selected from the groupconsisting of nitrogen, argon, helium, neon, or the like, or acombination thereof. The irradiation also can be carried out in avacuum.

In accordance with a preferred feature of this invention, theirradiation may be carried out in a sensitizing atmosphere. This maycomprise a gaseous substance which is of sufficiently small molecularsize to diffuse into the polymer and which, on irradiation, acts as apolyfunctional grafting moiety. Examples include substituted orunsubstituted polyunsaturated hydrocarbons; for example, acetylenichydrocarbons such as acetylene; conjugated or unconjugated olefinichydrocarbons such as butadiene and (meth)acrylate monomers; sulphurmonochloride, with chloro-tri-fluoroethylene (CTFE) or acetylene beingparticularly preferred. By “gaseous” is meant herein that thesensitizing atmosphere is in the gas phase, either above or below itscritical temperature, at the irradiation temperature.

Metal Piece: in accordance with the invention, the piece forming aninterface with polymeric, material is, for example, a metal. The metalpiece in functional relation with polyethylene, according to the presentinvention, can be made of a cobalt chrome alloy, stainless steel,titanium, titanium alloy or nickel cobalt alloy, for example. Variousmetal types can also be found in U.S. Ser. No. 60/424,709, filed Nov. 8,2002 (PCT/US03118053, filed Jun. 10, 2003, WO 2004000159).

Non-metallic Piece: In accordance with the invention, the piece formingan interface with polymeric material is, for example, a non-metal. Thenon-metal piece in functional relation with polyethylene, according tothe present invention, can be made of ceramic material, for example.

Interface: The term “interface” in this invention is defined as theniche in medical devices formed when an implant is in a configurationwhere a component is in contact with another piece (such as a metallicor a non-metallic component), which forms an interface between thepolymer and the metal or another polymeric material. For example,interfaces of polymer-polymer or polymer-metal are in medicalprosthesis, such as orthopedic joints and boric replacement parts, forexample, hip, knee, elbow or ankle replacements. Various metal/non-metaltypes and interfaces also can be found in U.S. Ser. No. 60/424,709,filed Nov. 8, 2002 (PCT/US03/18053, filed Jun. 10, 2003, WO 2004000159),the entirety of which is hereby incorporated by reference.

Inert Atmosphere: The term “inert atmosphere” refers to an environmenthaving no more than 1% oxygen and more preferably, an oxidant-freecondition that allows free radicals in polymeric materials to form crosslinks without oxidation during a process of sterilization. An inertatmosphere is used to avoid O₂, which would otherwise oxidize themedical device comprising a polymeric material, such as UHMWPE. Inertatmospheric conditions such as nitrogen, argon, helium, or neon are usedfor sterilizing polymeric medical, implants by ionizing radiation.

Inert atmospheric conditions such as nitrogen, argon, helium, neon, orvacuum are also used for sterilizing interfaces of polymeric-metallicand/or polymeric-polymeric in medical implants by ionizing radiation.

Inert atmospheric conditions also refers to a insert gas, inert fluid,or inert liquid medium, such as nitrogen gas or silicon oil.

Anoxic environment: “Anoxic environment” refers to an environmentcontaining gas, such as nitrogen, with less than 21%-22% oxygen,preferably with less than 2% oxygen. The oxygen concentration in ananoxic environment also can be at least 1%, 2%, 4%, 6%, 8%, 10%, 12%14%, 16%, 18%. 20%, or up to about 22%, or any integer or fractionalvalue thereabout or therebetween.

Vacuum: The term “vacuum” refers to an environment having no appreciableamount of gas, which otherwise would allow free radicals in polymericmaterials to form cross links without oxidation during a process ofsterilization. A vacuum is used to avoid O₂, which would otherwiseoxidize the medical device comprising a polymeric material, such asUHMWPE. A vacuum condition can be used for sterilizing polymeric medicalimplants by ionizing radiation.

A vacuum condition can be created using a commercially available vacuumpump. A vacuum condition also can be used when sterilizing interfaces ofpolymeric-metallic and/or polymeric-polymeric in medical implants byionizing radiation.

Residual Free Radicals: “Residual free radicals” refers to free radicalsthat are generated when a polymer is exposed to ionizing radiation suchas gamma or e-beam irradiation. While some of the free radicalsrecombine with each other to from crosslinks, some become trapped incrystalline domains. The trapped free radicals are also known asresidual free radicals.

According to one aspect of the invention, the levels of residual freeradicals in the polymer generated during an ionizing radiation (such asgamma or electron beam) is preferably determined using electron spinresonance and treated appropriately to reduce the free radicals throughrecombination.

Sterilization: One aspect of the present invention discloses a processof sterilization of medical implants containing polymeric material, suchas cross-linked UHMWPE. The process comprises sterilizing the medicalimplants by ionizing sterilization with gamma or electron beamradiation, for example, at a dose level ranging from about 25-70 kGy, orby gas sterilization with ethylene oxide or gas plasma.

Another aspect of the present invention discloses a process ofsterilization of medical implants containing polymeric material, such ascross-linked UHMWPE. The process comprises sterilizing the medicalimplants by ionizing sterilization with gamma or electron beamradiation, for example, at a dose level ranging from about 25-200 kGy.The dose level of sterilization is higher than standard levels used inirradiation. This is to allow cross-linking or further cross-linking ofthe medical implants during sterilization.

The term “alpha transition” refers to a transitional temperature and isnormally around 90-95° C.; however, in the presence of a sensitizingenvironment that dissolves in polyethylene, the alpha transition may bedepressed. The alpha transition is believed (An explanation of the“alpha transition temperature” can be found in Anelastic and DielectricAffects in Polymeric Solids, pages 141-143, by N. G. McCrum, B. E. Readand G. Williams; J. Wiley and Sons, N.Y., N.Y., published 1967) toinduce motion in the crystalline phase, which is hypothesized toincrease the diffusion of the sensitizing environment into this phaseand/or release the trapped free radicals. Heating above the alphatransition will also increase the diffusion of the additive, such asplasticizing agent or the antioxidant into the base polymer.

The term “critical temperature” corresponds to the alpha transition ofthe polyethylene. The term “below melting point” or “below the melt”refers to a temperature to below the melting point of a polyethylene,for example, UHMWPE. The term “below melting point” or “below the melt”refers to a temperature less than 155° C., which may vary depending onthe melting temperature of the polyethylene. The term “above meltingpoint” or “above the melt” refers to a temperature above the meltingpoint of a polyethylene, for example, UHMWPE. The term “above meltingpoint” or “above the melt” refers to a temperature more than 145° C.,which may vary depending on the melting temperature of the polyethylene.The melting temperature of the polyethylene can be, for example, 155°C., 145° C., 140° C. or 135° C., which again depends on the propertiesof the polyethylene being treated, for example, extended chain crystals,crystallinity, molecular weight averages and ranges, batch variations,etc. For example, “above melting point” or “above the melt” of apolymeric material under high pressure during a high-pressurecrystallization process refers to a temperature at or above 150° C. Themelting temperature is typically measured using a differential scanningcalorimeter (DSC) at a heating rate of 10° C. per minute. The peakmelting temperature thus measured is referred to as melting point andoccurs, for example, at approximately 137° C. for some grades of UHMWPE.It may be desirable to conduct a melting study on the startingpolyethylene material in order to determine the melting temperature andto decide upon an irradiation and annealing temperature.

The term “annealing” refers to heating the polymer above or below itspeak melting point. Annealing time can be at least 1 minute to severalweeks long. In one aspect the annealing time is about 4 hours to about48 hours, preferably 24 to 48 hours and more preferably about 24 hours.The annealing time required to achieve, a desired level of recoveryfollowing mechanical deformation is usually longer at lower annealingtemperatures. “Annealing temperature” refers to the thermal conditionfor annealing in accordance with the invention.

The term “contacted” includes physical proximity with or touching suchthat the sensitizing agent can perform its intended function.Preferably, a polyethylene composition or pre-form is sufficientlycontacted such that it is soaked in the sensitizing agent, which ensuresthat the contact is sufficient. Soaking is defined as placing the samplein a specific environment for a sufficient period of time at appropriatetemperature, for example, soaking the sample in a solution of anantioxidant. The environment is heated to a temperature ranging fromroom temperature to a temperature below the melting point of thematerial. The contact period ranges from at least about 1 minute toseveral weeks and the duration depending on the temperature of theenvironment.

The term “oxidation-resistant” refers to a state of polymeric materialhaving an oxidation index (A. U.) of less than about 0.5 following agingpolymeric materials for 5 weeks in air at 80° C. oven. Thus, anoxidation-resistant cross-linked polymeric material generally shows anA. U. of less than about 0.5 after the aging period.

“Oxidation index” refers to the extent of oxidation in polymericmaterial. Oxidation index is calculated by obtaining an infraredspectrum for the polymeric material and analyzing the spectrum tocalculate an oxidation index, as the ratio of the areas under the 1740cm⁻¹ carbonyl and 1370 cm⁻¹ methylene stretching absorbances aftersubtracting the corresponding baselines.

The term “Mechanical deformation” refers to deformation taking placebelow the melting point of the material, essentially ‘cold-working’ thematerial. The deformation modes include uniaxial, channel flow, uniaxialcompression, biaxial compression, oscillatory compression, tension,uniaxial tension, biaxial tension, ultra-sonic oscillation, bending,plane stress compression (channel die) or a combination of any of theabove. The deformation could be static or dynamic. The dynamicdeformation can be a combination of the deformation modes in small orlarge amplitude oscillatory fashion. Ultrasonic frequencies can be used.All deformations can be performed in the presence of sensitizing gasesand/or at elevated temperatures.

The term “deformed state” refers to a state of the polyethylene materialfollowing a deformation process, such as a mechanical deformation, asdescribed herein, at solid or at melt. Following the deformationprocess, deformed polyethylene at a solid state or at melt is be allowedto solidify/crystallize while still maintains the deformed shape or thenewly acquired deformed state.

“IBMA” refers to irradiation below the melt and mechanical annealing.“IBMA” also is referred to as “CIMA” (Cold Irradiation and MechanicallyAnnealed).

Sonication or ultrasonic at a frequency range between 10 and 100 kHz canbe used, with amplitudes on the order of 1-50 microns. The time ofsonication is dependent on the frequency and temperature of sonication.In one aspect, sonication or ultrasonic frequency ranged from about 1second to about one week, preferably about 1 hour to about 48 hours,more preferably about 5 hours to about 24 hours and yet more preferablyabout 12 hours.

The invention is further described by the following examples, which donot limit the invention in any manner.

Examples Example 1 Electron Beam Irradiation of Polyethylene forSterilization or Cross-Linking

Blocks or rods of UHMWPE were machined into 1 cm thick pieces. Thesesamples were irradiated using a 2.5 MeV an de Graff generator (e-beam)at Massachusetts Institute of Technology by passing under the electronbeam multiple times to achieve the desired radiation dose level(approximately 12.5 kGy per pass).

Example 2 Gamma Irradiation of Polyethylene for Sterilization orCross-Linking

Compression molded blocks (5.5×10×12 cm) were gamma irradiated using aCo⁶⁰ source (Sleds isomedix, Northhorough, Mass.).

Example 3 Blending with Vitamin E Powder and Irradiation Above theMelting Point of UHMWPE

UHMWPE blocks blended with 0, 0.05, 0.1, 0.3 and 1.0 wt/wt % vitamin Eare irradiated to 0, 65, 100, 150 and 200-kGy by gamma or e-beamirradiation above the melting point of UHMWPE, at about 170° C.

Example 4 Irradiation Followed by High Pressure Crystallization by RouteI and Route II

Compression molded GUR1050 UHMWPE blocks (5.5×10×12 cm) were gammairradiated to 65 kGy in air.

Route I: One 2″ dia. cylinder was machined from an irradiated block andplaced in a pressure chamber, where it was heated to 200° C. in waterand held for 5 hours. Then, the pressure was increased to 380 MPa andthe sample was held at this temperature and pressure for 5 hours.Finally, the sample was cooled to room temperature and the pressure wassubsequently released.

Route II: Another 2″ dia. cylinder was placed in a pressure chamber,where it was pressurized to 380 MPa in water first, then heated to 200°C. and held for 5 hours. Finally, the sample was cooled to roomtemperature and the pressure was subsequently released.

Differential scanning colarimetry (DSC) was used to measure thecrystallinity of the polyethylene test samples. The DSC specimen wasweighed with a Sartorius CP 225D balance to a resolution of 001milligrams and placed in an aluminum sample pan. The pan was crimpedwith an aluminum cover and placed in a TA instruments Q-1000Differential Scanning Calorimeter. The sample and the reference werethen heated at a heating rate of 10° C./min from −20° C. to 160° C.,cooled to −20° C. and subjected to another heating cycle from −20° C. to160° C. at 10° C./min. Heat flow as a function of time and temperaturewas recorded and the cycles are referred to as 1^(st) heat, 1^(st) cooland 2^(nd) heat, respectively.

Crystallinity was determined by integrating the enthalpy peak from 20°C. to 160° C., and normalizing it with the enthalpy of melting of 100%crystalline polyethylene, 291 J/g.

Dogbone specimens were tested to determine mechanical properties perASTM D-638 using a MTS II machine (Eden Prarie, Minn.) at a crossheadspeed of 10 mm/min.

Route II resulted in the formation of extended chain crystals. The DSCanalysis showed the presence of high temperature (142° C.) meltingcrystals in the 65-kGy irradiated and HPC treated polyethylene, usingboth Route I and Route II (see FIG. 3). The increase in peak meltingtemperature from 132° C. to 142° C. indicates the formation of extendedchain crystals for irradiated UHMWPE during HPC treatment. Thecrystallinity of 65-kGy irradiated polyethylene was 57±1%, whichincreased to 63±1% after Route I HPC treatment, and to 59±2% after RouteII HPC treatment.

Irradiated and HPC-treated UHMWPE by Route I had no detectable freeradicals. Irradiated and HPC-treated UHMWPE by Route II had reduced orno detectable free radicals.

The mechanical properties of 65-kGy irradiated HPC-treated UHMWPEs arereported in Table 1.

TABLE 1 Tensile mechanical properties of UHMWPE. WF (kJ/m²) UTS (MPa)EAB (%) 65-kGy HPC Route I 1474 ± 65  48 ± 2 246 ± 11 65-kGy HPC RouteII 1631 ± 423 47 ± 8 301 ± 22

Example 5 Wear Rate of HPC-Treated Vitamin E-Blended UHMWPE

Ram extruded GUR1050 UHMWPE was used as control. GUR1050 UHMWPE powderwas mixed with vitamin E (D,L-α-tocopherol, >98%) to 5 wt/wt %. Then,the mixture was diluted with UHMWPE powder to 0.1 wt/wt % vitamin F inUHMWPE. The mixture was compression molded into blocks (5.5×10×12 cm),which were machined to 2″ diameter before high pressure crystallization(HPC). HPC was carried out in a custom-built one liter high pressurechamber. A 2″ dia, cylinder was placed in the pressure chamber, where itwas heated to 180° C. in water and held for 5 hours. Then, the pressurewas increased to 310 MPa and the sample was held at this temperature andpressure for 5 hours. Finally, the sample was cooled to room temperatureand the pressure was subsequently released. As controls, virgin UHMWPE,0.1 wt % blended UHMWPE, virgin UHMWPE HPC-treated in the same mannerwere used.

Pins machined from the above described samples (diameter 9 mm, length 13mm. n≧3) were tested on a custom-built bi-directional POD wear tester ata frequency of 2 Hz. Bovine calf serum was used as lubricant andquantified wear gravimetrically at 0.5 million-cycle intervals until 2million cycles (MC).

HPC treated 0.1 wt % vitamin-UHMWPE blend showed significantly lowerwear than the virgin UHMWPE while HPC treatment in the absence ofvitamin E increased the wear rate of UHMWPE (see Table 2).

TABLE 2 Wear rate of virgin and HPC treated UHMWPEs. Wear rate (mg/MC)Virgin 7.4 ± 2.2 HPC 13.4 ± 0.4  0.1 wt % HPC 5.1 ± 1.1

Example 6 Mechanical Properties of HPC-Treated, Vitamin E-Blended UHMWPE

Ram extruded GUR1050 UHMWPE was used as control. GUR1050 UHMWPE powderwas mixed with vitamin E (D,L-α-tocopherol, >98%) to 5 wt/wt %. Then,the mixture was diluted with UHMWPE powder to 0.1, 0.3, and 1.0 wt/wt %vitamin E in UHMWPE. The mixture was compression molded into blocks(5.5×10×12 cm), which were machined to 2″ diameter before high pressurecrystallization (HPC). HPC was carried out in a custom-built one literhigh pressure chamber. A 2″ dia. cylinder was placed in the pressurechamber, where it was heated to 180° C. in water and held for 5 hours.Then, the pressure was increased to 310 MPa and the sample was held atthis temperature and pressure for 5 hours. Finally, the sample wascooled to room temperature and the pressure was subsequently released.As controls, virgin UHMWPE, and virgin UHMWPE HPC-treated in the samemanner were used.

Differential scanning colarimetry (DSC) was used to measure thecrystallinity of the polyethylene test samples. The DSC specimen wasweighed with a Sartorius CP 225D balance to a resolution of 0.01milligrams and placed in an aluminum sample pan. The pan was crimpedwith an aluminum cover and placed in a TA instruments Q-1000Differential Scanning Calorimeter. The sample and the reference werethen heated at a heating rate of 10° C./min from −20° C. to 160° C.,cooled to −20° C. and subjected to another heating cycle from −20° C. to160° C. at 10° C./min. Heat flow as a function of time and temperaturewas recorded and the cycles are referred to as 1^(st) heat, 1^(st) cooland 2^(nd) heat, respectively.

Crystallinity was determined by integrating the enthalpy peak from 28°C. to 160° C., and normalizing it with the enthalpy of melting of 100%crystalline polyethylene, 291 J/g.

Dogbone specimens were tested to determine mechanical properties perASTM D-638 using a MTS II machine (Eden Prarie, Minn.) at a crossheadspeed of 10 mm/min.

The crystallinity of UHMWPE was improved from 70% to 76% with theaddition of 0.1 wt % vitamin E. No significant difference was noted inthe crystallinity of high pressure to crystallized polyethylenes thathad been blended with higher concentrations of Vitamin E (p>0.1, seeTable 3).

The ultimate tensile strength of 0.1 wt % vitamin E blended, highpressure crystallized UHMWPE was significantly higher than virgin, highpressure crystallized (HPC) UHMWPE (p=0.012, Table 3), which was nottrue at higher concentrations of vitamin E.

TABLE 3 Tensile mechanical properties of UHMWPEs. EAB Crystallinity UTSYS WF (%) (%) (MPa) (MPa) (kJ/m²) Untreated Virgin 484 ± 29 59 ± 2 51 ±3 21 ± 1 2589 ± 156 HPC treated Virgin 361 ± 31 70 ± 1 56 ± 6 24 ± 22281 ± 392 0.1 wt % 373 ± 11 76 ± 1 66 ± 2 28 ± 1 3219 ± 186 0.3 wt %376 ± 25 76 ± 1 50 ± 6 25 ± 3 1905 ± 348 1.0 wt % 391 ± 23 74 ± 2 51 ± 324 ± 2 2020 ± 223

The synergistic effect of vitamin E and HPC on UHMWPE at a vitamin Bconcentration of 0.1 wt/wt %, resulted not only in low wear, but also ina ‘super-tough’ UHMWPE with very high work-to-failure (Table 3).

Example 7 Morphological Characterization of HPC-Treated, VitaminE-Blended UHMWPEs

Ram extruded GUR1050 UHMWPE was used as control. GUR1050 UHMWPE powderwas mixed with vitamin E (D,E-α-tocopherol, >98%) to 5 wt/wt %, Then,the mixture was diluted with UHMWPE powder to 0.1, 0.3, and 1.0 wt/wt %vitamin E in UHMWPE. The mixture was compression molded into blocks(5.5×10×12 cm), which were machined to 2″ diameter before high pressurecrystallization (HPC), HPC was carried out in a custom-built one literhigh pressure chamber. A 2″ dia. cylinder was placed in the pressurechamber, where it was heated to 180° C. in water and held for 5 hours.Then, the pressure was increased to 310 MPa and the sample was held atthis temperature and pressure for 5 hours. Finally, the sample wascooled to room temperature and the pressure was subsequently released.As controls, virgin UHMWPE, and virgin UHMWPE HPC-treated in the samemanner were used.

Freeze-fractured surfaces were gold-coated (Edward Sputtercoater S150B)and electron microscopy images were obtained by using a FM/Phillips XL30FEG ESEM (Hillsboro, Oreg.).

SEM images revealed abundant voids in all HPC-treated samples except 0.1wt % vitamin F-blended sample (see FIGS. 4( a-d)), which were notobserved in any of the non-HPC-treated samples (see FIGS. 5( a-d)). Thecavities might have formed as a result of melting and re-crystallizationof larger crystals under pressure or displacement of vitamin E duringrecrystallization. There appear to be competing mechanisms where effectsof higher crystallinity are balanced out by the effects of voids ataround 0.1 wt % vitamin E concentration.

Example 8 Doping and Homogenization of HPC-Treated UHMWPE

Ram extruded GUR1050 UHMWPE was used. A 2″ dia. cylinder was placed inthe pressure chamber, where it was heated to 180° C. in water and heldfor 5 hours. Then, the pressure was increased to 310 MPa (45,000 psi)and the sample was held at this temperature and pressure for 5 hours.Finally, the sample was cooled to room temperature and the pressure wassubsequently released. This 2″ diameter high pressure crystallized blockwas machined into 1 cm-thick sections and irradiated at room temperatureby electron-beam irradiation to 125 kGy using a 2.5 MeV van de Graffgenerator at Massachusetts Institute of Technology by passing under thebeam multiple times to achieve the desired dose (approximately 12.5 kGyper pass).

One 1 cm-thick section was cut in two. One piece was doped withα-tocopherol at 120° C. for 5 hours, it was then taken out ofα-tocopherol, coiled down to room temperature, wiped clean with cottongauze and placed in a convection oven at 120° C. for 64 hours. The otherpiece was doped with a-tocopherol at 124° C. for 5 hours, it was thentaken out of α-tocopherol, cooled down to room temperature, wiped cleanwith cotton gauze and placed in a convection oven at 124° C. for 64hours.

The α-tocopherol profiles in these two samples were measured by infraredspectroscopy as described in Example 9. The samples were cut in half andsectioned (150 μm). Infrared spectra were collected by a BioRad UMA 500microscope with an aperture size of 50×50 μm as a function of depth awayfrom the free surface of the original sample.

An α-tocopherol index was calculated as the ratio of the areas under the1265 cm⁻¹ α-tocopherol and 1895 cm⁻¹ polyethylene skeletal absorbances.

The α-tocopherol profiles of high pressure crystallized, 125 kGyirradiated, α-tocopherol-doped and homogenized UHMWPE samples are shownin FIG. 6. The lowest index level attained in the sample doped andannealed at 120° C. was 0.016 and the lowest index level attained in thesample doped and annealed at 124° C. was 0.069.

Example 9 Measurement of Antioxidant Diffusion into Polyethylene

To measure the diffusion profile of the antioxidant in the test samplesthat were doped in α-tocopherol, a cross-section was cut out of thedoped section (100-150 μm) using an LKB Sledge Microtome. The thincross-section was then analyzed using a BioRad UMA 500 infraredmicroscope (Natick, Mass.). Infrared spectra were collected with anaperture size of 50×50 μm as a function of depth away from one of theedges that coincided with the free surface of the sample that contactedthe antioxidant during immersion. The absorbance between 1226 and 1295cm⁻¹ is characteristic of α-tocopherol and polyethylene does not absorbnear these frequencies. For polyethylene, the 1895 cm⁻¹ wave number forthe CH₂ rocking mode is a typical choice as an internal reference. Thenormalized value, which is the ratio of the integrated absorbances of1260 cm⁻¹ and 1895 cm⁻¹, is an index that provides a relative metric ofα-tocopherol composition in polyethylene and is known as theα-tocopherol (vitamin E) index.

Example 10 Blending Followed by High Pressure Crystallization by RouteII Followed by Irradiation Followed by High Pressure Crystallization byRoute I

Ram extruded GUR1050 UHMWPE is used as control. GUR1050 UHMWPE powder ismixed with vitamin E (D,L-α-tocopherol, >98%) to 5 wt/wt %. Then, themixture is diluted with UHMWPE powder to 0.1 wt/wt % vitamin E inUHMWPE. The mixture is compression molded into blocks (5.5×10×12 cm),which are machined to 2″ diameter before high pressure crystallization(HPC) HPC is carried out in a custom-built one liter to high pressurechamber. A 2″ dia. cylinder is placed in the pressure chamber, where thepressure is increased to 310 MPa (45,000 psi) in water and then heatedto 180° C. The block is held at this temperature and pressure for 5hours. Finally, the sample is cooled to room temperature and thepressure is subsequently increased. The high pressure crystallized blockis irradiated to 100-kGy. Then it is placed in the high pressurechamber, where it is heated is to 180° C. in water and held for 5 hours.Then the pressure is increased to 310 MPa (45,000 psi) and the sample isheld at this temperature and pressure for 5 hours, Finally, the sampleis cooled to room temperature and the pressure is subsequently released.

Example 11 Blending Followed by High Pressure Crystallization by RouteII Followed by Irradiation Followed by High Pressure Crystallization byRoute II

Ram extruded GUR1050 UHMWPE is used as control. GUR1050 UHMWPE powder ismixed with vitamin E (D,L-α-tocopherol, >98%) to 5 wt/wt %. Then, themixture is diluted with UHMWPE powder to 0.1 wt/wt % vitamin E inUHMWPE. The mixture is compression molded into blocks (5.5×10×12 cm),which are machined to 2″ diameter before high pressure crystallization(HPC), HPC is carried out in a custom-built one liter high pressurechamber. A 2″ dia. cylinder is placed in the pressure chamber, where thepressure is increased to 310 MPa (45,000 psi) in water and then heatedto 180° C. The block is held at this temperature and pressure for 5hours. Finally, the sample is cooled to room temperature and thepressure is subsequently released. The high pressure crystallized blockis irradiated to 100-kGy. Then it is placed in the pressure chamber,where the pressure is increased to 310 MPa (45,000 psi) in water andthen heated to 180° C. The block is held at this temperature andpressure for 5 hours. Finally, the sample is cooled to room temperatureand the pressure is subsequently released.

Example 12 Wear Rate of Vitamin E-Blended, Irradiated and High PressureCrystallized UHMWPE

Ram extruded GUR1050 UHMWPE is used as control. GUR1050 UHMWPE powder ismixed with vitamin E (D,L-α-tocopherol, >98%) to 5 wt/wt %. Then, themixture is diluted with UHMWPE powder to 0.1 wt/wt % vitamin E inUHMWPE. The mixture is compression molded into blocks (5.5×10×12 cm),which are machined to 2″ diameter before high pressure crystallization(HPC). HPC is carried out in a custom-built one liter high pressurechamber. A 2″ dia. cylinder is placed in the pressure chamber, where itis heated to 200° C. in water and held for 5 hours. Then, the pressureis increased to 380 MPa (55,000 psi) and the sample is held at thistemperature and pressure for 5 hours. Finally, the sample is cooled toroom temperature and the pressure is subsequently released.

Pins machined from the above described samples (diameter 9 mm, length 13mm, n≦3) are tested on a custom-built bi-directional POD wear tester ata frequency of 2 Hz. We use bovine calf serum as lubricant and quantifywear gravimetrically at 0.5 million-cycle intervals until 2 millioncycles (MC).

By using high pressure crystallization on vitamin F-blended cross-linkedUHMWPE, a wear-resistant UHMWPE is obtained.

Example 13 Improved Mechanical Strength of High Pressure Crystallized,Slow Irradiated and Melted UHMWPE

Ram extruded GUR1050 UHMWPE was used as stock. A 2″ dia, cylinder wasplaced in the pressure chamber, where it was heated to 180° C. in waterand held for 5 hours. Then, the pressure was increased to 310 MPa(45,000 psi) and the sample was held at this temperature and pressurefor 5 hours. Finally, the sample was cooled to room temperature and thepressure was subsequently released. This 2″ diameter high pressurecrystallized block was machined into 1 cm-thick sections and irradiatedat room temperature by electron-beam irradiation to 150 kGy using a 2.5MeV an de Graff generator at Massachusetts Institute of Technology bypassing under the beam multiple times to achieve the desired dose(approximately 12.5 kGy per pass). One cm-thick section was irradiatedto 150 kGy at approximately 4 kGy/pass. One 1 cm-thick sectionirradiated to 150 kGy at 12.5 kGy/pass was melted at 170° C. in vacuumafter irradiation.

Dogbone specimens were tested to determine mechanical properties perASTM D-638 using a MTS II machine (Eden Prarie, Minn.) at a crossheadspeed of 10 mm/min.

The ultimate tensile strength of irradiated samples was reduced comparedto high pressure crystallized samples (see Table 4). However, both slowirradiation and melting after irradiation increased the strength ofirradiated HPC UHMWPE.

TABLE 4 Crystallinity and mechanical strength of high pressurecrystallized and irradiated UHMWPEs Sample Crystallinity (%) UTS (MPa)Conventional UHMWPE 61 ± 2 51 ± 5 HPC UHMWPE 75 ± 2 56 ± 6 150-kGyirradiated HPC UHMWPE 79 ± 1 28 ± 4 150-kGy irradiated HPC UHMWPE 59 ± 136 ± 1 and melted 150-kGy irradiated HPC UHMWPE — 36 (slow irradiation)100 kGy irradiated and melted 58 ± 1 28 ± 2 UHMWPE (CISM)

This effect is due to the tie molecules between crystallites beingplaced under tension after HPC; and during irradiation of thetie-molecules. As a result, they became more prone to chain scissionunder tension. This tensioning would then adversely affect the fractureof the tie-molecules during mechanical testing. Both slow irradiationand melting allowed these taut-tie molecules to relax, improvingmechanical strength.

Example 14 Improved Mechanical Strength of High Pressure Crystallized,Slow-Irradiated and Annealed UHMWPE

Ram extruded GUR1050 UHMWPE is used as stock. A 2″ dia. cylinder wasplaced in the pressure chamber, where it is heated to 180° C. in waterand held for 5 hours. Then, the pressure is increased to 310 MPa (45,000psi) and the sample is held at this temperature and pressure for 5hours. Finally, the sample is cooled to room temperature and thepressure is subsequently released. The 2″ diameter high pressurecrystallized block is machined into 1 cm-thick sections and irradiatedat room temperature by electron-beam irradiation to 150 kGy using a 15MeV van de Graff generator at Massachusetts Institute of Technology bypassing under the beam multiple times to achieve the desired dose(approximately 4 kGy per pass). One cm-thick sections irradiated to 150kGy are thermally annealed at 100° C., 120° C. and 136° C. in vacuumafter irradiation to improve mechanical properties.

Example 15 Vitamin E

Vitamin E (Acros™ 99% D-a-Tocopherol, Fisher Brand), was used in theexperiments described herein, unless otherwise specified. The vitamin Eused is very light yellow in color and is a viscous fluid at roomtemperature. Its melting point is 2-3° C.

Example 16 Bi-Directional Pin-on-Disk (POD) Wear Testing

The wear rate was quantified on a number of UHMWPE test samples thatwere subjected to various processing steps as described in some of theexamples below. For this, the wear behavior of the UHMWPE sample wastested using cylindrical shaped samples (9 mm diameter and 13 mm height)on a custom-built bi-directional pin-on-disk (POD) wear tester at afrequency of 2 Hz. Bovine calf serum was used as lubricant andquantified wear is gravimetrically at 0.5 million-cycle intervals.Initially, the pins were subjected to 200,000 cycles of POD testing toremove reach a steady state wear rate independent of diffusion orasperities on the surface. Three pins from each group were tested for atotal of 2 million cycles. The wear rate was calculated as the linearregression of wear vs. number of cycles from 0.2 to 2 million cycles.

Example 17 Determination of Crystallinity with Differential ScanningCalorimetry

The crystallinity was quantified on a number of UHMWPE test samples thatwere subjected to various processing steps as described in some of theexamples below. For this, differential scanning colarimetry (DSC) wasused to measure the crystallinity of the polyethylene test samples. TheDSC specimens were weighed with a Sartorius CP 225D balance to aresolution of 0.01 milligrams and placed in an aluminum sample pan. Thepan was crimped with an aluminum cover and placed in a TA instrumentsQ-1000 Differential Scanning Calorimeter. The samples and the referencewere then heated at a heating rate of 10° C./min from −20° C. to 160° C.cooled to −20° C. and subjected to another heating cycle from −20° C. to160° C. at 10° C./min, Heat flow as a function of time and temperaturewas recorded and the cycles are referred to as 1^(st) heat, 1^(st) cooland 2^(nd) heat, respectively.

Crystallinity was determined by integrating the enthalpy peak from 20°C. to 160° C., and normalizing it with the enthalpy of melting of 100%crystalline polyethylene, 291 J/g.

Example 18 Dimensional Stability of Irradiated and High PressureCrystallized (Route II) Acetabular Liner

An acetabular liner machined of 100-kGy irradiated and melted GUR1050UHMWPE was placed in a pressure chamber, where it was pressurized to 380MPa (55,000 to psi) in water first, then heated to 200° C. and held for5 hours. Finally, the sample was cooled to room temperature and thepressure was subsequently released.

The dimensions of the liner were measured by a coordinate measuringmachine (CMM, Global A2, Brown & Sharpe, North Kingstown R.I.) beforeand after high pressure crystallization. Table 5 shows that thedimensional changes on the articular and backsides of the liner wereminimal because melting was avoided. Overall, this HPC-treated liner wasvery stable.

TABLE 5 Dimensional stability of a 100-kGy irradiated and meltedacetabular liner high pressure crystallized at 55,000 psi and 200° C. byRoute II. Inner Diameter (mm) Outer Diameter (mm) Pre-HPC 36.128 ± 0.00042.275 ± 0.001 Post-HPC 36.099 ± 0.002 42.231 ± 0.003 Change −0.029−0.044

Example 19 Morphological Characterization of UHMWPE Blended with 0.1 wt% α-Tocopherol and High Pressure Crystallized by Route I by TransmissionElectron Microscopy (TEM)

Ram extruded GUR1050 UHMWPE: was used as control. GUR1050 UHMWPE powderwas mixed with vitamin E (D,L-α-tocopherol, >98%) to 5 wt/wt %. Then,the mixture was diluted with UHMWPE powder to 0.1 wt/wt % vitamin E inUHMWPE. The mixture was compression molded into blocks (5.5×10×12 cm),which were machined to 2″ diameter before high pressure crystallization(HPC). HPC was carried out in a custom-built one liter high pressurechamber. A 2″ dia. cylinder was placed in the pressure chamber, where itwas heated to 200° C. in water and held for 5 hours. Then, the pressurewas increased to 380 MPa (55,000 psi) and the sample was held at thistemperature and pressure for 5 hours. Finally, the sample was cooled toroom temperature and the pressure was subsequently released.

A sample cut from the highly crystalline bar was etched by heating inchlorosulfonic acid at 60° C. for 6 hours, washed in sulfuric acid andwater. It was microtomed, stained with a uranyl acetate solution andimaged at 100 kV accelerating voltage on a Philips 420T.

0.1 wt % α-tocopherol blended and high pressure crystallized UHMWPEclearly exhibited the presence of ‘extended chain crystals’.

It is to be understood that the description, specific examples and data,while indicating exemplary embodiments, are given by way of illustrationand are not intended to limit the present invention. Various changes andmodifications within the present invention will become apparent to theskilled artisan from the discussion, disclosure and data containedherein, and thus are considered part of the invention.

1-5. (canceled)
 6. A method of making highly crystalline polymericmaterial comprising: a) doping the polymeric material with an additiveby introducing the additive into the polymeric material, wherein thepolymeric material is in the form of a consolidated stock, resin powder,flakes, particles, powder, or a mixture thereof; b) heating thepolymeric material to a temperature of above the melting point of thepolymeric material; c) pressuring the heated polymeric material at about10-1000 MPa; d) holding at this pressure and temperature; e) cooling theheated polymeric material to a temperature below the melting point ofthe polymeric material; and f) releasing the pressure, thereby forming ahighly crystalline polymeric material.
 7. (canceled)
 8. A method ofmaking cross-linked highly crystalline polymeric material comprising: a)doping the polymeric material with an additive by introducing theadditive into the polymeric material, wherein the polymeric material isin the form of a consolidated stock, resin powder, flakes, particles,powder, or a mixture thereof; b) heating the polymeric material to atemperature of above the melting point of the polymeric material andpressuring the heated polymeric material at about 10-1000 c), holding atthis pressure and temperature; d) cooling the heated polymeric materialto a temperature below the melting point of the polymeric material; e)releasing the pressure, thereby forming a highly crystalline polymericmaterial; and f) irradiating the highly crystalline polymeric materialwith ionizing radiation, thereby forming a highly crystallinecross-linked polymeric material. 9-11. (canceled)
 12. A method of makinghighly crystalline polymeric material comprising: a) doping thepolymeric material with an additive by introducing the additive into thepolymeric material, wherein the polymeric material is in the form of aconsolidated stock, resin powder, flakes, particles, powder, or amixture thereof; b) annealing the polymeric material below or above themelt; c) heating the polymeric material to a temperature of above themelting point of the polymeric material and pressuring the heatedpolymeric material under at least about 10-1000 MPa; d) holding at thispressure and temperature; e) cooling the heated polymeric material to atemperature below the melting point of the polymeric material; and f)releasing the pressure, thereby forming a highly crystalline polymericmaterial.
 13. (canceled)
 14. A method of making highly crystallinecross-linked polymeric material comprising: a) doping the polymericmaterial with an additive by introducing the additive into the polymericmaterial, wherein the polymeric material is in the form of aconsolidated stock, resin powder, flakes, particles, powder, or amixture thereof; b) annealing the polymeric material below or above themelt;; c) heating the polymeric material to a temperature of above themelting point of the polymeric material and pressuring the heatedpolymeric material about 10-1000 MPa; d) holding at this pressure andtemperature; e) cooling the heated polymeric material to a temperaturebelow the melting point of the polymeric material; f) releasing thepressure, thereby forming a highly crystalline polymeric material; andg) irradiating the highly crystalline polymeric material with ionizingradiation, thereby forming a cross-linked highly crystalline polymericmaterial. 15-17. (canceled)
 18. The method according to claim 6, whereinthe polymeric material is a polyolefin, a polypropylene, a polyamide, apolyether ketone, or a mixture thereof.
 19. The polyolefin of claim 18is selected from a group consisting of a low-density polyethylene,high-density polyethylene, linear low-density polyethylene, ultra-highmolecular weight polyethylene (UHMWPE), or a mixture thereof.
 20. Themethod according to claim 8, wherein the irradiation is carried out inan atmosphere containing between about 1% and about 22% oxygen.
 21. Themethod according to claim 8, wherein the irradiation is carried out inan inert atmosphere, wherein the inert atmosphere contains gas selectedfrom the group consisting of nitrogen, argon, helium, neon, or the like,or a combination thereof.
 22. The method according to claim 8, whereinthe irradiation is carried out in a vacuum.
 23. The method according toclaim 8, wherein the polymeric material is irradiated at a temperatureabove or below the melting point of the polymeric material.
 24. Themethod according to claim 8, wherein the irradiation dose is more-thanabout 1 kGy to 1000 kGy, or more.
 25. The method according to claim 8,wherein the radiation dose is between about 25 and about 1000 kGy. 26.The method according to claim 8, wherein the irradiation dose is about25 kGy to 400 kGy.
 27. The method according to claim 8, wherein theirradiation dose is at least about 150 kGy.
 28. The method according toclaim 8, wherein the radiation dose is about 65 kGy, about 75kGy, orabout 150 kGy.
 29. The method according to claim 8, wherein theradiation is a gamma irradiation.
 30. The method according to claim 8,wherein the radiation is an electron beam irradiation.
 31. The methodaccording to claim 6, wherein the polymeric material is pressurized toat least about 150 MPa, 200 MPa, 250 MPa, 300 MPa, 310 MPa, 320 MPa, 380MPa, 400 MPa, or 450 MPa.
 32. The method according to claim 6, whereinthe additive is vitamin E.
 33. The method according to claim 32, whereinthe vitamin E concentration is between 0.0001 wt/wt % to 50 wt/wt %. 34.The method according to claim 6, wherein the doping is carried out in aninert gas or air.
 35. The method according to claim 12, wherein theannealing is carried out in inert gas or air.
 36. The method accordingto claim 6, wherein the doping is carried out under pressure in an inertgas or air.
 37. The method according to claim 12, wherein the annealingis carried out under pressure in inert gas or air.
 38. The methodaccording to claim 6, wherein the pressurized cross-linked polymericmaterial is heated to a temperature below 150° C.
 39. The methodaccording to claim 6, wherein the polymeric material is irradiated at atemperature between about room temperature and about 90° C.
 40. Themethod according to claim 8, wherein the polymeric material isirradiated at a temperature between about 90° C. and the melting pointof the polymeric material.
 41. The method according to claim 8, whereinthe polymeric material is irradiated at a temperature above or below themelting point of the polymeric material.
 42. The method according toclaim 8, wherein the highly crystalline polymeric material is irradiatedat a temperature between about 90° C. and the peak melting point of thehighly crystalline polymeric material.
 43. A medical implant comprisingthe polymeric material according to claim
 6. 44. (canceled)
 45. Themethod according to claim 6, wherein the polymeric material iscompression molded to another piece or a medical implant, therebyforming an interface or an interlocked hybrid material.
 46. The methodaccording to claim 6, wherein the doping is carried out by soaking themedical implant in the antioxidant for about an hour or about 16 hours.47. The method according to claim 43, wherein the medical implant ispackaged and sterilized by ionizing radiation or gas sterilization,thereby forming a sterile and highly crystalline cross-linked medicalimplant.
 48. The method according to claim 8, wherein the additive-dopedhighly crystalline polymeric material is machined thereby forming amedical implant, this medical implant is packaged and sterilized byionizing radiation or gas sterilization, thereby forming a sterile andadditive-doped highly crystalline cross-linked medical implant.
 49. Themethod according to claim 43, wherein the implant comprises medicaldevices selected from the group consisting of acetabular liner, shoulderglenoid, patellar component, finger joint component, ankle jointcomponent, elbow joint component, wrist joint component, toe jointcomponent, bipolar hip replacements, tibial knee insert, tibial kneeinserts with reinforcing metallic and polyethylene posts, intervertebraldiscs, sutures, tendons, heart valves, stents, vascular grafts. 50-52.(canceled)
 53. The method according to claim 6, wherein doping iscarried out at a temperature below or above the melt.
 54. The methodaccording to claim 12, wherein annealing is carried out at a temperaturebelow or above the melt.
 55. A medical implant comprising the polymericmaterial made according to claim
 6. 56. A medical implant comprising thepolymeric material made according to claim
 8. 57. (canceled)
 58. Amedical implant comprising the polymeric material made according toclaim
 12. 59. (canceled)
 60. A medical implant comprising the polymericmaterial made according to claim
 14. 61. A medical implant comprisingthe polymeric material made according to claim
 70. 62. A medical implantcomprising the polymeric material made according to claim
 71. 63. Amedical implant comprising the polymeric material made according toclaim
 72. 64-69. (canceled)
 70. A method of making highly crystallineblend of cross-linked polymeric material comprising: a) blending thepolymeric material with one or more additives; b) heating the blend to atemperature above the melting point and pressurizing the blend, whereinthe pressurizing can be carried out prior to heating; c) holding at atemperature that is above the melting temperature of the polymericmaterial and at a pressure that is between 1000 MPa and an ambientpressure; d) cooling the heated blend; e) releasing the pressure,thereby forming a highly crystalline blend of polymeric material; and f)irradiating the highly crystalline blend of polymeric material withionizing radiation at a temperature that is above the room temperatureand below the melting point of the highly crystalline blend of polymericmaterial, thereby forming highly crystalline blend of cross-linkedpolymeric material.
 71. A method of making highly crystalline blend ofcross-linked interlocked hybrid material comprising: a) blending thepolymeric material with one or more additives, thereby forming apolymeric blend; b) contacting the polymeric blend to the counterface ofa second material, thereby forming a hybrid material; c) heating thehybrid material to a temperature above the melting point of thepolymeric material, and pressurizing the hybrid material, wherein thepressurizing can be carried out prior to heating, thereby forming ahighly crystalline blend of interlocked hybrid material having aninterface between the polymeric blend and the second material; d)holding the interlocked hybrid material at the pressure and temperature;e) cooling the heated blend of interlocked hybrid material; f) releasingthe pressure, thereby forming a highly crystalline blend of interlockedhybrid material; and g) irradiating the interlocked hybrid material withionizing radiation at a temperature that is above the room temperatureand below the melting point of the highly crystalline blend, therebyforming a highly crystalline blend of cross-linked and interlockedhybrid material.
 72. A method of making a cross-linked polymericmaterial comprising: a) blending a polymeric material with one or moreadditives, thereby forming a polymeric blend; b) consolidating thepolymeric blend, thereby forming a consolidated polymeric material; c)irradiating the consolidated polymeric material at a temperature belowor above the melting point of the polymeric material with ionizingradiation, thereby forming a cross-linked polymeric material; d)mechanically deforming the cross-linked polymeric material, therebyreducing residual free radicals; and e) annealing the mechanicallydeformed, cross-linked polymeric material at a temperature below themelting point of the mechanically deformed, cross-linked polymericmaterial, thereby forming a cross-linked polymeric material havingreduced residual free radicals.
 73. The method according to claim 55,wherein the medical implant sterilized by ionizing radiation or gassterilization by gas plasma or ethylene oxide, thereby forming a sterileand highly crystalline cross-linked medical implant.
 74. The methodaccording to claim 72, wherein the annealed cross-linked polymericmaterial is machined, thereby forming a medical implant,
 75. The methodaccording to claim 58, wherein the medical implant is packaged andsterilized by ionizing radiation or gas sterilization, thereby forming asterile and additive-doped highly crystalline cross-linked medicalimplant.
 76. The method according to claim 12, wherein annealing iscarried out in air for at least for one minute to about 5 hours or moreat about 130° C. temperature.
 77. The method according to claim 72,wherein the additive is vitamin E.
 78. The method according to claim 77,wherein the vitamin E concentration is between 0.01 wt/wt % to below 50wt/wt %.
 79. The method according to claim 77, wherein the vitamin Econcentration is between 0.1 wt/wt % and 0.2 wt %.
 80. The methodaccording to claim 72, wherein the radiation dose is between about 25kGy and about 500 kGy.
 81. The method according to claim 72, wherein theirradiation dose is about 100 kGy, about 150 kGy, about 175 kGy, orabout 200 kGy.
 82. The method according to claim 72, wherein thecross-linked polymeric material is mechanically deformed uniaxially. 83.The method according to claim 72, wherein the cross-linked polymericmaterial is mechanically deformed to a compression ratio of about 2.5 ata temperature of about 130° C.
 84. The method according to claim 72,wherein the cross-linked polymeric material is heated to a temperaturebetween above the room temperature and below the melt, and thenmechanically deformed.
 85. The method according to claim 72, wherein thecross-linked polymeric material is heated to a temperature of about 130°C., and then mechanically deformed.
 86. The method according to claim72, wherein the additive is an antioxidant.
 87. The method according toclaim 72, wherein the polymeric blend contains a mixture ofantioxidants.
 88. The method according to claim 87, wherein one of theantioxidants is alpha-tocopherol.
 89. A method of making cross-linkedhighly crystalline polymeric material comprising: a) doping thepolymeric material with an additive by introducing the additive into thepolymeric material, wherein the polymeric material is in the form of aconsolidated stock; b) heating the polymeric material to a temperatureof above the melting point of the polymeric material and pressuring theheated polymeric material at about 10-1000 MPa; c) holding at thispressure and temperature; d) cooling the heated polymeric material to atemperature below the melting point of the polymeric material; e)releasing the pressure, thereby forming a highly crystalline polymericmaterial; and f) irradiating the highly crystalline polymeric materialwith ionizing radiation, thereby forming a highly crystallinecross-linked polymeric material.
 90. A method of making cross-linkedhighly crystalline polymeric material comprising: a) doping thepolymeric material with an additive by introducing the additive into thepolymeric material, wherein the polymeric material is in the form of aresin powder, flakes, particles, powder, or a mixture thereof; b)heating the polymeric material to a temperature of above the meltingpoint of the polymeric material and pressuring the heated polymericmaterial at about 10-1000 MPa; c) holding at this pressure andtemperature; d) cooling the heated polymeric material to a temperaturebelow the melting point of the polymeric material; e) releasing thepressure, thereby forming a highly crystalline polymeric material; andf) irradiating the highly crystalline polymeric material with ionizingradiation, thereby forming a highly crystalline cross-linked polymericmaterial.